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- Herausgeber: Thieme Medical Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
<p><strong><em>A practical, reader-friendly guide for dental students on the neuroscience of the orofacial region</em></strong></p> <p>Understanding neural mechanisms that control orofacial pain, proper masticatory function, taste, speech, swallowing, and proprioceptive input to the temporomandibular joint and teeth is an important facet of dentistry. <cite>Neuroscience of Dentistry</cite> by renowned educators Barbara J. O'Kane and Laura C. Barritt provides foundational knowledge on these topics. The text integrates fundamental concepts of general neuroscience with vital information on neural mechanisms of the orofacial region and associated pain pathways.</p> <p>The book is organized in two parts covering basic neuroscience and orofacial neuroscience. Part one is subdivided into four units on the central nervous system, brain and spinal cord gross anatomy, sensory systems, and motor systems. Part two features three units focused on orofacial structures and tissues, dental structures, and orofacial pain and anesthesia. Each generously illustrated, succinctly written, and consistently formatted chapter includes an introductory overview and learning objectives.</p> <p><strong>Key Highlights</strong></p> <ul> <li>Throughout the book, relevant clinical correlations emphasize the relationship between basic neuroscience and clinical practice</li> <li>Concise, high-yield illustrations, schematics, charts, and tables enhance understanding of general and orofacial neuroanatomy concepts</li> <li>Helpful overviews at the beginning of each chapter highlight key concepts</li> <li>National board style questions at the end of each chapter emphasize board-relevant information that enables self-study</li> </ul> <p>This is a must-have resource for dental students taking neuroscience during their first or second year of dental school. It will also benefit other health science and dental hygiene students, as well as oral and maxillofacial surgery residents.</p> <p>This book includes complimentary access to a digital copy on <a href="https://medone.thieme.com/">https://medone.thieme.com</a>.</p>
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Veröffentlichungsjahr: 2022
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Neuroscience for Dentistry
Barbara J. O’Kane, MS, PhD
Professor
Department of Oral Biolog
Creighton University School of Dentistry
Omaha, Nebraska, USA
Laura C. Barritt, PhD
Professor and Chair
Department of Oral Biology
Creighton University School of Dentistry
School of Dentistry
566 illustrations
ThiemeNew York • Stuttgart • Delhi • Rio de Janeiro
Library of Congress Cataloging-in-Publication Data is available from the publisher.
Illustrations by Voll M and Wesker K. From:Schuenke M, Schulte E, Schumacher U, THIEME Atlas of Anatomy.
© 2022. Thieme. All rights reserved.
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ISBN: 978-1-62623-781-0
Also available as an e-book:
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To my children and grandchildren, especially the girls…..#s♀em.
Barbara J. O’Kane, MS, PhD
To my husband, Steve, for his patience and support. To my family for their encouragement. And in memory of my father.
Laura C. Barritt, PhD
Contents
Preface
Acknowledgments
Contributors
Part A Basic Neuroscience
Unit I Central Nervous System
1Organization of the Nervous System
1.1Overview of the Nervous System
1.2The Central Nervous System
1.3The Peripheral Nervous System
Questions and Answers
2Development of the Nervous System
2.1Overview of Nervous System Development
2.2Spinal Cord Differentiation
2.3Brain Differentiation
2.4Development and Derivatives of the Rhombencephalon
Questions and Answers
3Neurohistology
3.1Classification of Cells of the Nervous System
3.2Neurons
3.3Classification of Neurons in the Nervous System
3.4Neuroglial Cells
3.5Histological Appearance of CNS
Questions and Answers
4Neurophysiology
Gilbert M. Willett
4.1Neurophysiology Overview
4.2Cell Membrane
4.3Action Potentials
4.4Synapses
4.5Neurotransmitters and Receptors
4.6Clinical Correlations
Questions and Answers
Unit II Gross Anatomy of Brain and Spinal Cord
5Gross Topography of the Brain
5.1Overview
5.2Neuroanatomical Terms
5.3Telencephalon
5.2Neuroanatomical Terms
5.3Telencephalon
5.4Diencephalon
5.5Mesencephalon
5.6Metencephalon
5.7Myelencephalon
5.8Medial Surface of the Cerebral Hemispher
5.9Inferior Aspect of the Cerebral Hemispheres
Questions and Answers
6Blood Supply of the Brain
6.1Overview of the Blood Supply to the Brain
6.2Anterior Circulation of the Brain
6.3Posterior Circulation of the Brain
6.4Circle of Willis
6.5Blood–Brain Barrier
6.6Venous Drainage in the Brain
Questions and Answers
7Ventricles and Cerebrospinal Fluid (CSF)
7.1Overview of the Ventricles and CSF
7.2Ventricles
7.3Flowof CSF through the Ventricular System
7.4Choroid Plexus and CSF
Questions and Answers
8The Meninges
8.1Overview of the Meninges
8.2Meningeal Layers
8.3Function of the Meninges
8.4Dural Septa
8.5Dural Sinuses
8.6Blood Supply to the Meninges
8.7Innervation of the Meninges
Questions and Answers
9Cranial Nerves
9.1Overview of Cranial Nerves
9.2Functional Modalities of Cranial Nerves
9.3Summary of Cranial Nerve
9.4Summary of Cranial Nerve Testing
Questions and Answers
10Gross Anatomy of the Spinal Cord
10.1Overview of the Spinal Cord
10.2Organization of the Spinal Cord
10.3Gross Anatomy of the Spinal Cord
10.4Internal Anatomy of the Spinal Cord
10.5Meninges
10.6Blood Supply to the Spinal Cord
Questions and Answers
Unit III Sensory Systems
11Anatomical Receptors and Nerve Fibers
11.1Overview of Anatomical Rece
11.2Sensory Reception and Transduction
11.3Stimulus (Sensory) Modalities
11.4Somatosensory Receptor Classification
11.5Cutaneous Receptors of theOralMucosa
Questions and Answers
12Somatosensory Systems Part I—Somatosensory Pathways of Body
12.1Overview of Ascending Somatosensory System
12.2Transmission of Conscious and Unconscious Sensations
12.3Anterolateral System
12.4Dorsal Column-Medial Lemniscus (DCML) Pathway
12.5Spinocerebellar System
Questions and Answers
13Somatosensory Systems Part II—Somatosensory Pathways of Head
13.1Overview of Somatosensory Innervation of the Head
13.2Trigeminal Nuclear Complex
13.3Trigeminal Somatosensory Pathways
13.4Sensory Contributions from Facial, Glossopharyngeal, and Vagus Nerves
Questions and Answers
14Pain
14.1Overview of Pain
14.2Classification of Pain
14.3Pain Receptors and Afferents
14.4Physiology of Pain
14.5Mechanisms of Pain Modulation
14.6Descending Pathways of PainModulation
14.7Acute versus Chronic Pain
14.8Differences in Pain Perception
Questions and Answers
15Special Senses
15.1Special Visceral Afferents (SVA)
15.2Special Somatic Afferents (SSA)
Questions and Answers
Unit IV Motor Systems
16Direct Activation Pathways
16.1Overview of Direct Motor Pathways
16.2Motor Neurons
16.3Corticospinal Tract
16.4Corticobulbar Tract
16.5Disorders of the Motor System
16.6Spinal Reflexes
Questions and Answers
17Indirect Activation Pathways
17.1Overview of Indirect Influences on Movement
17.2Brainstem Nuclei and Tracts
17.3Basal Ganglia
17.4Cerebellum
Questions and Answers
18Integrated Systems
18.1Autonomic Nervous System (ANS)
18.2Hypothalamus
18.3Limbic System
18.4Reticular Formation
Questions and Answers
Part B Orofacial Neuroscience
Unit V Review of Orofacial Structures and Tissues
19Development and Organization of Oropharyngeal Region
19.1OverviewofOropharyngeal Development
19.2OverviewofOral Cavity andOralMucosa
19.3Structures of Oral Vestibule
19.4Structures of the Oral Cavity Proper
19.5Structures of Pharyngeal Region
19.6Structures of the Larynx
Questions and Answer
20Overview of Orofacial Pathways Part I – Trigeminal and Facial Nerves
20.1Introduction
20.2Trigeminal Nerve: Overview of Functional Components
20.3Facial Nerve
Questions and Answers
21Overview of Orofacial Pathways Part II—Glossopharyngeal, Vagus, and Hypoglossal Nerves
21.1Introduction
21.2Glossopharyngeal
21.3Vagus
21.4Hypoglossal
Questions and Answers
22Neuromuscular Control of Mastication, Swallowing, and Speech
22.1Overview of Oropharyngeal Region
22.2Summary of Neural Control Mechanisms
22.3Neural Reflexes of Oromotor System
22.4Mastication
22.5Swallowing
22.6Speech Production
Questions and Answers
Unit VI Dental-Related Structures
23Temporomandibular Joint
Gilbert M. Willett
23.1Overviewof the Temporomandibular Joint
23.2Anatomy Overview
23.3TMJ Sensory (Afferent) Innervation
23.4TMJ Neuromuscular Control
23.5Common Temporomandibular Joint–Related Disorders and Differential Diagnosis Clinical Correlation Examples
Questions and Answers
24Salivary Glands
24.1Overview of the Salivary Glands
24.2Anatomical Overview of Major and Minor Salivary Glands
24.3Saliva Production, Composition, and Flow Rates
24.4NeuralMediated Salivary Reflex Pathways
Questions and Answers
25Teeth
25.1Anatomical and Structural Components of Teeth
25.2Periodontium
25.3Dental Pulp
25.4Trigeminal Pathway
Questions and Answers
Unit VII Orofacial Pain and Dental Anesthesia
26Orofacial Pain
26.1Overview of Orofacial Pain Pathways
26.2Nociceptive Orofacial Pain
26.3Neuropathic Orofacial Pain
Questions and Answers
27Local Anesthesia: Intraoral Injections Margaret A. Jergenson
27.1Overview of Dental Local Anesthesia
27.2Mandibular Local Anesthesia
27.3Maxillary Local Anesthesia
Questions and Answers
Appendix: Compilation of Muscles Involved in Chapter 22
Index
Preface
Practicing dentists are concerned with neural mechanisms controlling orofacial pain, masticatory function, taste, and proprioceptive input to the temporomandibular joint (TMJ) and teeth. As a result, one of the primary objectives of a dental neuroscience course should be to instruct the motor, sensory, and autonomic innervation of the head and neck pathways as well as the fundamentals of the biology and management of orofacial pain.
Most neuroscience textbooks provide excellent content coverage but do not focus on head and neck neuroscience from a dental medicine perspective and, although suitable for most health care students, the content does not adequately target dental students. The lack of specific dental information in neuroscience textbooks requires instructors, students, and practitioners to integrate information from multiple sources in order to develop a clear and comprehensive understanding of the orofacial region. Because of this, we set out to create a textbook that emphasizes the importance of the orofacial region and presents dental applicable information in the context of fundamental neuroscience.
Neuroscience for Dentistry is a unique textbook that integrates fundamental concepts of general neuroscience with essential information on the neural mechanisms involved in the orofacial region and orofacial pain pathways. The text is arranged in two sections. Part I provides a concise overview of general neuroanatomy and targets all health science students enrolled in a first-year neuroscience course. Part II focuses specifically on the neural mechanisms that regulate mastication, speech, swallowing, as well as proprioceptive input from the muscles, joints, and periodontal ligament. Detailed information on the cranial nerves is provided, with specific emphasis on orofacial pain pathways, pain modulation, and pain control. The focus on orofacial neuroscience and orofacial pain is a distinctive attribute of Neuroscience for Dentistry and it addresses the fundamental need for a neuroscience textbook that is tailored to dental students, students of dental hygiene, and residents in oral maxillofacial surgery.
Although the textbook is written for dental students, it can also be used to teach neuroanatomy to other health science students or serve as a reference for dental practitioners and residents. To facilitate multidisciplinary use, the text is structured so that individual units and selected chapters can be used independently.
Key features of Neuroscience for Dentistry include:
•Presentation of essential concepts of general and orofacial neuroanatomy through concise, high-yield descriptions and illustrations.
•Schematics, charts, and tables to augment the concepts presented in the text.
•Each chapter provides an introductory overview of chapter content and learning objectives.
•National board style questions at the end of each chapter emphasize board-relevant information and allow for self-study.
•Relevant clinical correlations are integrated throughout the textbook to emphasize the relationship between basic neuroscience and clinical disorders.
Barbara J. O'Kane, MS, PhD
Laura C. Barritt, PhD
Acknowledgments
This book would not have been possible without the help of many dedicated individuals. We offer special thanks to our talented colleagues, Drs. Margaret A. Jergenson and Gilbert M. Willett, for providing their expertise and contributing the chapters on Neurophysiology, Temporomandibular Joint, and Local Anesthesia: Intraoral Injections. We are grateful to the many colleagues and students who gave insightful feedback, suggestions, and honest critique of the chapters. Additionally, we thank our editors for their guidance and support. We also acknowledge Thieme's group of medical illustrators who created new art to complement the existing illustrations from Thieme's extensive collection. Many of the images that enhance the chapters of this book are from the award-winning three-volume Thieme Atlas of Anatomy and Gilroy's Anatomy: An Essential Textbook with illustrations by Markus Voll and Karl Wesker.
Barbara J. O'Kane, MS, PhD
Laura C. Barritt, PhD
Contributors
Margaret A. Jergenson, DDS
Professor
Department of Oral Biology
Creighton University School of Dentistry
Omaha, Nebraska, USA
Gilbert M. Willett, PT, MS, PhD
Associate Professor
Department of Oral Biology
Creighton University School of Dentistry
Omaha, Nebraska, USA
Part ABasic Neuroscience
Unit ICentral Nervous System
1Organization of the Nervous System
2Development of the Nervous System
3Neurohistology
4Neurophysiology
1 Organization of the Nervous System
1.1 Overview of the Nervous System
The nervous system is anatomically divided into the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS is made up of the brain and spinal cord. The PNS consists of both cranial and spinal nerves that act as conduits for information travelling between the body and the CNS. The PNS can be functionally subdivided into sensory and motor components. The motor division of the PNS is subdivided into the somatic nervous system that primarily controls voluntary activities and the visceral efferent nervous system that primarily controls involuntary activities. The visceral motor system is also called the autonomic nervous system (ANS). It has two branches: the sympathetic nervous system and parasympathetic system (Fig. 1.1).
Fig. 1.1 The nervous system is divided into the central (CNS) and peripheral (PNS) nervous systems. The CNS consists of the brain and spinal cord, which constitute a functional unit. The PNS consists of the nerves emerging from the brain and spinal cord (cranial and spinal nerves, respectively).
1.2 The Central Nervous System
•The CNS is composed of the brain and spinal cord (Fig. 1.2).
Fig. 1.2 The central nervous system (CNS) is composed of the brain and spinal cord. (Reproduced with permission from Gilroy AM, MacPherson BR. Atlas of Anatomy. Third Edition. © Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
•The brain can be divided into the following major structures: cerebrum, brainstem, and cerebellum (Fig. 1.2).
Fig. 1.3 Midsagittal section of adult brain showing the right hemisphere. (Reproduced with permission from Gilroy AM, MacPherson BR. Atlas of Anatomy. Third Edition. © Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
•The cerebrum is made up of two cerebral hemispheres, each containing several lobes.
•The midbrain, pons, and medulla make up the brainstem.
•The cerebellum has lobes and hemispheres as well as a midline structure known as the vermis.
•The brain resides in the cranium while the spinal cord is contained within the vertebral column.
•The function of the CNS is to process and coordinate information that is received from the body and then direct the appropriate responses necessary for the maintenance of normal activity.
•The CNS is composed of neurons (Fig. 1.4a, b), which transmit impulses and neuroglial cells (Fig. 1.4c), which perform a more supportive function in maintaining homeostasis. Neuroglia do not transmit impulses
Fig. 1.4 (a) Structure of a neuron (multipolar). (b) Pseudounipolar (sensory) neuron. (c) Neuroglial cells found in the central nervous system. (Reproduced with permission from Michael J, Sircar S. Fundamentals of Medical Physiology. © Thieme 2011.)
•The gray and white matter of the CNS is largely made up of the cell bodies of neurons and the myelinated axons of neurons, respectively (Fig. 1.5).
Fig. 1.5 Gray and white matter in the spinal cord as seen in cross section. (Reproduced with permission from Gilroy AM, MacPherson BR. Atlas of Anatomy. Third Edition. © Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
1.3 The Peripheral Nervous System
•The PNS is made up of 12 cranial nerves (Fig. 1.6a) and 31 pairs of spinal nerves (Fig. 1.6b).
Fig. 1.6 (a) Cranial nerves from inferior (basal) view. The 12 pairs of cranial nerves (CN) are numbered according to the order of their emergence from the brainstem. Note: The sensory and motor fibers of the cranial nerves enter and exit the brainstem together (in contrast to spinal nerves, whose sensory and motor fibers enter and leave through posterior and anterior roots, respectively).
(b) Spinal nerves: 31 pairs of nerves emerge from the spinal cord. Spinal nerves contain both sensory and motor fibers that emerge from the spinal cord as separate roots and unite to form the mixed nerve. In certain regions, the spinal nerves may combine to form plexuses (e.g., cervical, brachial, or lumbosacral). (Reproduced with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Third Edition, Vol 1. © Thieme 2020. Illustrations by Markus Voll and Karl Wesker.)
•The main function of the PNS is to connect the CNS to the rest of the body. Sensory receptors, which are specialized structures in the periphery, detect stimuli (e. g., heat, pain, touch) which are transmitted to the CNS via peripheral nerves.
•The PNS can be functionally divided into sensory and motor divisions (Fig. 1.1).
•The sensory division is also called the afferent division. It carries sensory information picked up by the receptors in the periphery and takes it into the CNS.
•The motor division is referred to as the efferent division. It carries signals from the CNS to its targets such as muscles, viscera, and glands.
•The sensory and motor divisions of the PNS are further subdivided into somatic and visceral components (Fig. 1.1).
•The somatic afferent (sensory) division carries sensory information produced in somatic structures such as skin, muscles, bones, and joints.
•The visceral afferent (sensory) division carries sensory information generated in viscera such as the heart, lungs, and gastrointestinal tract.
•The somatic efferent (motor) division carries signals from the CNS to somatic structures. The result is contraction of muscles that are under voluntary control as well as those muscles that are involved in somatic reflexes.
•The visceral efferent (motor) division, or the ANS, carries impulses to glands, cardiac muscle, and smooth muscle.
•The visceral motor arm of the PNS (ANS) has two components: the sympathetic nervous system and the parasympathetic system (Fig. 1.1).
•The sympathetic nervous system is referred to as the “fight or flight” response and is associated with situations that are perceived as potentially harmful to the body.
•The parasympathetic system is called the “rest and digest” response because it returns the body back to the homeostatic state.
•Nerves of the PNS can carry either motor or sensory information but the majority carry both types and therefore are called mixed nerves (Fig. 1.7).
Fig. 1.7 Spinal cord segment. The spinal cord consists of 31 segments, each innervating a specific area of the skin (a dermatome) of the head, trunk, or limbs. Afferent (sensory) posterior rootlets and efferent (motor) anterior rootlets form the posterior and anterior roots of the spinal nerve for that segment. The two roots fuse to form a mixed (motor and sensory) spinal nerve that exits the intervertebral foramen and immediately thereafter divides into an anterior and posterior ramus. (Reproduced with permission from Gilroy AM, MacPherson BR. Atlas of Anatomy. Third Edition. © Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
•Mixed spinal nerves are formed by the joining of a dorsal root (sensory fibers) and a ventral root (motor fibers).
•The dorsal root exits the spinal cord from the dorsal aspect of the gray matter, the dorsal horn which carries sensory information. Sensory cell bodies are located in the dorsal root ganglion (DRG).
•The ventral root exits the spinal cord from the ventral aspect and carries motor information. The cell bodies for the ventral root are located in the ventral aspect of the gray matter known as the ventral horn.
•The dorsal root and ventral root join together just distal to the DRG to form a mixed spinal nerve.
•Cranial nerves emerge from nuclei or collections of neuronal cell bodies in the brain, and can be sensory, motor, or both (mixed).
Questions and Answers
1.Which of the following divisions of the nervous system carries signals from the periphery into the CNS?
a)Motor
b)Sensory
c)Efferent
d)Sympathetic
Level 1: Easy
Answer B: The sensory division carries information into the CNS. (A) Motor division carries information from CNS to target. (C) Motor information is carried on efferent fibers. (D) The sympathetic division is part of the ANS and is motor/efferent
2.The targets of the sensory somatic afferent division of the nervous system include which of the following?
a)Skin
b)GI tract
c)Glands
d)Smooth muscle
Level 2: Moderate
Answer A: Skin is innervated by the somatic afferent division. (B) Viscera are innervated by visceral afferent division. (C) Glands are innervated by the visceral afferent division. (D) Smooth muscle is innervated by the visceral afferent division.
3.The sympathetic nervous system can be described as:
a)Part of the PNS
b)Visceral motor division
c)Part of the ANS
d)Visceral efferent division
e)All of the above are correct
Level 2: Moderate
Answer E: The sympathetic nervous system can be described as all of the above.
4.The CNS is composed of which of the following structures?
a)Brain
b)Spinal nerves
c)Cranial nerves
d)Ganglia
Level 1: Easy
Answer A: The CNS is composed of the brain and spinal cord. (B) Spinal nerves, (C) Cranial nerves, and (D) Ganglia are all part of the PNS.
5.Mixed spinal nerves consist of which of the following?
a)Sensory fibers
b)Motor fibers
c)Dorsal root
d)Ventral root
e)All of the above are correct
Level 2: Moderate
Answer E: All of the structures listed make up a mixed spinal nerve.
2 Development of the Nervous System
Learning Objectives
1.Compare the marginal layer of the neural tube to the mantle layer.
2.Describe the neural crest derivatives that may be associated with the somatic sensory nervous system; the derivatives associated with the autonomic nervous system; and the derivatives associated with the adrenal gland and skin.
3.Describe the adult derivatives of the secondary vesicles.
4.Compare the function and location of the alar and basal plate in the spinal cord.
5.Explain the potential outcome that results from a failure of neural crest cells to migrate.
6.Explain the potential outcome that results from a failure of neuroblasts to migrate from the ventricular zone during cortical development.
2.1 Overview of Nervous System Development
2.1.1 Introduction
Development of the central and peripheral nervous system begins in the third week of embryonic development due to inductive signals originating from the notochord (axial mesoderm). Signaling molecules secreted from the notochord induces a portion of the overlying ectoderm to differentiate into neuroectoderm and form the neural plate. This is followed by neurulation which is the process by which the neural plate folds inward and then fuses to form the neural tube. The central nervous system differentiates from the neural tube, whereas the peripheral nervous system develops from neural crest cells that originate from the dorsal margin of the neural tube. Failure for neurulation to occur properly leads to several pathological conditions that may impact fetal development.
2.1.2 Neural Tube Development
Primary and Secondary Neurulation
•Differential growth of the neural plate results in upward growth and inward folding of the lateral edges of the neural plate to form the neural folds. The center of the neural plate invaginates downward, forming the neural groove (Fig. 2.1a, b).
Fig. 2.1 (a–d) Process of neurulation. Schematic diagram demonstrating the stages of neurulation leading to the development of the central (CNS) and peripheral nervous system (PNS). Dorsal view of embryo (a,c); cross-section of embryo (b,d). The neural tube develops from the neural plate on the dorsal surface of the embryo. A central groove initially develops in the neural plate forming the neural groove. Neural crest cells migrate from the free edge of the groove as the neural groove fuses together, and the closed neural tube separates from the overlying ectoderm. The brain and spinal cord differentiate from the neural tube, whereas neural structures associated with PNS develop from neural crest cells.
•During neurulation, the dorsal margins of the neural folds begin to fuse in the midline, converting the neural groove into the neural tube. As the neural folds begin to fuse, neural crest cells separate from the free edge and migrate away from the neural tube (Fig. 2.1c, d).
•The neural tube continues to fuse along the craniocaudal axis and becomes separated from the surface ectoderm. Two openings, known as anterior and posterior neuropores, initially remain open on the cranial (rostral) and caudal ends of the fused neural tube and then close during the fourth week. Failure of the neural tube to fuse properly leads to neural tube defects.
•The expanded cranial portion of the neural tube gives rise to the brain and the caudal portion gives rise to the spinal cord. The lumen of the tube, known as the neural canal, persists and develops into the ventricles of the brain and central canal of the spinal cord.
•In the caudal end of the neural tube, a solid cell mass known as the conus medullaris appears on day 20. The conus medullaris forms a central cavity and then fuses with the terminal end of the neural tube to form the distal portion of the spinal cord in a process known as secondary neurulation.
Clinical Correlation Box 2.1: Neural Tube Defects
Neural tube defects occur when various parts of the neural tube fail to fuse.
•Anencephaly is a lethal condition in which a significant portion of the brain and skull fail to develop. It results from a failure of the anterior neuropore to fuse.
•A persistent opening in the posterior neuropore causes spina bifida. The severity depends on the length and position of the defect. Severe forms, such as spina bifida cystica, are associated with neurological defects and herniation of the spinal cord through the vertebral arches due to the incomplete development of the spinal cord, meninges, and vertebrae.
•Tethered cord syndrome is a disorder associated with the tethering (fixation) of the caudal spinal cord tissue that results in limited movement of the spinal cord within the vertebral column. Clinical presentations include, but are not limited to, gait abnormalities, foot and spinal deformities, and urinary tract issues.
Neural Crest Formation and Migration (Table 2.1)
Table 2.1 Neural crest derivatives
Cranial region
Cardiac region
Trunk/Body
•Ectomesenchyme skeletal and connective tissue of pharyngeal arches
•Odontoblasts of the teeth
•Cementoblasts of the teeth
•Parafollicular cells of thyroid gland
•Cranial sensory ganglia neurons
•Autonomic ganglia neurons
•Leptomeninges (pia-arachnoid)
•Cells of aorticopulmonary septum of heart
•Melanocytes of the epidermis
•Spinal sensory ganglia neurons
•Autonomic ganglia of body
•Enteric ganglia neurons
•Chromaffin cells of adrenal medulla
•Schwann cells of PNS
•Satellite cells of PNS
Abbreviation: PNS, peripheral nervous system.
•Neural crest cells develop from the dorsal surface of the neural folds and detach as the neural tube starts to fuse. Neural crest cells migrate away from the neural tube along specific routes and populate the developing head, heart, and trunk, where they differentiate into a variety of structures (Fig. 2.2).
Fig. 2.2 Development of the neural crest cells. Main migratory pathways and derivatives of the neural crest cell.
•Defects in neural crest migration lead to a variety of developmental disorders including craniofacial abnormalities.
○Cranial neural crest cells
–Neural crest cells move cranially toward the head and neck and contribute to neurons of the cranial sensory ganglia and autonomic ganglia of the peripheral nervous system.
–The two inner meningeal layers collectively referred to as the leptomeninges, consisting of arachnoid and pia, are also derived from cranial neural crest cells.
–In addition, cranial neural crest cells combine with mesenchyme in developing pharyngeal arch region to form neural crest–derived ectomesenchyme. Ectomesenchyme forms the connective tissue and skeletal derivatives of the head and neck, including the dentin and cementum of the teeth.
○Cardiac neural crest cells
–Neural crest cells migrate toward the cardiac region to aid in the development and septation of the heart and great vessels.
•Trunk neural crest cells
•Neural crest cells migrate caudally to the trunk (body) and give rise to neurons of the peripheral spinal sensory ganglia (dorsal root ganglia), enteric ganglia of the gastrointestinal tract, autonomic ganglia of the autonomic nervous system, and chromaffin cells of the adrenal medulla.
•In addition, neural crest cells migrate throughout the developing embryo and differentiate into melanocytes associated with the epidermis of the skin and supportive neuroglial cells, such as satellite and Schwann cells of the peripheral nervous system.
Clinical Correlation Box 2.2: Neural Crest Defects
Abnormalities in the proliferation, migration, and survival of neural crest cells gives rise to numerous syndromes and disorders including aorticopulmonary septal defects and craniofacial abnormalities
•DiGeorge syndrome is a primary immunodeficiency disease that results from abnormal neural crest cell migration to the head, neck, and cardiac region. Clinical manifestations include increased susceptibility to infection due to congenital absence of the thymus, disruption in the formation of the parathyroid gland, as well as cardiac abnormalities associated with aorticopulmonary septal defects.
•Treacher Collins syndrome results from a failure of neural crest cell to migrate to the region of the developing face, leading to craniofacial abnormalities involving the growth and development of the bones of the face. Patients exhibit hypoplasia of the maxilla and mandible, as well as abnormalities in the external ear.
•Hirschsprung disease results from abnormal migration of neural crests cell to the wall of the colon and the failure of the enteric and autonomic ganglion cells to differentiate. Patients exhibit intestinal blockage resulting from impaired peristalsis.
Cranial Sensory Placodes (Fig. 2.3)
•During the fourth week of embryonic development, a series of bilateral ectodermal thickenings, known as neurogenic placodes, develop in a craniocaudal sequence from the region surrounding the anterior neural plate and cranial neural crest cells. The cranial placodes fall into two broad categories: neurogenic and non-neurogenic placodes.
Fig. 2.3 Cranial sensory placode formation. Cranial sensory placodes develop as bilateral ectodermal thickenings and differentiate into two groups, neurogenic or non-neurogenic placodes. Neurogenic placodes give rise to special sensory neurons and neuroepithelium that mediate olfaction, hearing, and balance (purple). An additional group of neurogenic placodes develops from ectoderm and neural crest into the sensory neurons associated with cranial sensory ganglia (V, VII, IX, and X) (red). Non-neurogenic placodes develop from ectoderm and give rise to the optic (lens) and anterior pituitary gland (yellow). (Modified with permission from Greenstein B, Greenstein A. Neuroanatomy and Neurophysiology. © Thieme 2000.)
•Neurogenic placodes give rise to neurons associated with the special sensory systems involved in smell and sight.
•Olfactory (Nasal) placode differentiate into the bipolar neurosensory epithelial cells of the olfactory nerve (CN I) and induce the development of the olfactory bulbs.
•Otic placodes develop into the neurosensory epithelial cells and non-neural epithelium associated with the cochlea and vestibular end organs of the inner ear and neurons of the vestibulocochlear ganglion (CV VII).
•The second group of neurogenic placodes differentiates into neurons associated with the cranial sensory ganglia (CN V, VII, IX, and X) of the developing pharyngeal arches in the head and neck region. These placodes develop from ectoderm and neural crest–derived cells and include:
•Trigeminal placodes form neurons of the trigeminal ganglion that provide cutaneous sensory innervation to the face and jaw.
•Epibranchial placodes develop in association with CNVII, IX, X and are associated with visceral sensory neurons of the geniculate, petrosal, and nodose (inferior) ganglia, respectively. These neurons innervate taste buds and visceral organs.
•Two additional ectodermal placodes develop but give rise to non-neurogenic structures:
•Optic (lens) placodes—differentiate to form the lens epithelium of the eye. The optic placode develops in association with the optic cup, a neural outgrowth from the developing brain, which gives rise to the retina.
•Adenohypophyseal placode (anterior pituitary glands)—differentiates from a thickening of ectoderm in the oral cavity known as Rathke pouch and forms the anterior pituitary gland. The anterior pituitary gland will fuse with the posterior lobe which differentiates from the diencephalon.
Neural Tube Morphogenesis (Table 2.2)
Table 2.2 Derivatives of brain vesicles
Three primary vesicles
Five secondary vesicles
Derivatives of vesicle wall
Derivatives of cavities
Prosencephalon (forebrain)
Telencephalon
Cerebral hemispheres
Lateral ventricles
Diencephalon
Thalamus
Third ventricle
Mesencephalon (midbrain)
Mesencephalon
Midbrain
Cerebral aqueduct
Rhombencephalon (hindbrain)
Metencephalon
Pons
Cerebellum
Cranial (rostral) part fourth ventricle
Myelencephalon
Medulla oblongata
Caudal part fourth ventricle
•During the fourth and fifth week of embryonic development, rapid cellular proliferation within the walls of the neural tube results in hollow swellings, or brain vesicles forming in the rostral end of the neural tube. As the developing brain vesicles rapidly enlarge, folds or flexures form in the rostral neural tube which will enable the developing skull to accommodate the expanding brain. The developing spinal cord develops from the distal portion of the neural tube.
•Primary Vesicle and Flexure Development of the Brain (Fig. 2.4).
Fig. 2.4 (a,b) Primary brain vesicle formation (dorsal view, neural tube cut open). Three primary vesicles develop from the rostral end of the neural tube due to rapid cellular proliferation. The primary vesicles will give rise to the neural tissue of the forebrain, midbrain, and hindbrain. The spinal cord develops from caudal portion of the neural tube. (Reproduced with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Second Edition, Vol 3. ©Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
•During the fourth week of development, cranial expansion of the wall of the neural tube leads to the development of three distinct primary brain vesicles:
-Prosencephalon (forebrain).
-Mesencephalon (midbrain).
-Rhombencephalon (hindbrain).
•At the primary vesicle stage, two curvatures, the cephalic and cervical flexures, develop in the rostral neural tube (Fig. 2.5).
Fig. 2.5 Development of cephalic and cervical flexures. As the brain vesicles expand, the embryo folds forming two flexures: a cephalic (mesencephalic) flexure develops in the midbrain and the second flexure develops at the junction of the hindbrain and spinal cord, as the cervical flexure. (Reproduced with permission from Gilroy AM, MacPherson BR. Atlas of Anatomy. Third Edition. © Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
○The cephalic (mesencephalic) flexure develops initially as a ventral fold at the level of the midbrain.
○The second curvature, known as the cervical flexure, develops on the ventral surface at the junction of the hindbrain and spinal cord.
•Secondary vesicle and ventricle development of the brain.
○During the end of the fifth week, the three primary vesicle walls continue to expand and become subdivided into five secondary brain vesicles. Concomitantly, the lumen of the rostral neural tube dilates to form a series of four interconnected ventricles (cavities) containing cerebrospinal fluid.
○The choroid plexus, which is a vascular network consisting of ependymal cells, develops from the roof of each ventricle and functions in the production of cerebrospinal fluid. The ventricular system communicates with the central canal of the spinal cord, facilitating the circulation of cerebrospinal fluid.
•The five secondary brain vesicles include (Fig. 2.6):
Fig. 2.6 Development of secondary brain vesicles and ventricular systems. The three primary vesicles expand and subdivide to form secondary vesicles. The forebrain differentiates into the telencephalon and diencephalon associated with the future cerebral cortex. The hindbrain differentiates into two structures: the metencephalon and myelencephalon. The metencephalon forms the pons and cerebellum. The myelencephalon differentiates into the medulla. As the vesicles differentiate, the lumen of rostral neural tube dilates to form four interconnected cavities known as ventricles that become filled with cerebrospinal fluid (CSF). (Reproduced with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Second Edition, Vol 3. ©Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
•The prosencephalon vesicle divides into the telencephalon and diencephalon.
-The walls of telencephalon continue to expand to form two lateral outgrowths, which become the primitive cerebral hemispheres. A ventral outgrowth gives rise to the olfactory bulb.
-In the region of the telencephalon, the ventricle dilates and splits to form the two lateral ventricles.
-The diencephalon gives rise to bilateral outgrowths which form the optic vesicles, and a ventral evagination, known as the infundibular stalk and neurohypophysis (posterior pituitary). A midline dilation of the lumen in the region of the diencephalon forms the third ventricle.
-The lateral ventricles of the telencephalon connect to the third ventricle of the diencephalon through the interventricular foramina (of Monroe).
○The mesencephalon remains unchanged, but a narrow groove, the rhombencephalic isthmus, develops and separates the mesencephalon from the rhombencephalon.
–The lumen of the mesencephalon narrows to form the cerebral aqueduct that connects the third and fourth ventricles.
•The rhombencephalon divides into secondary vesicles known as the metencephalon and myelencephalon.
•The pons and cerebellum differentiate from the metencephalon, and the medulla oblongata develops from the myelencephalon.
•As the secondary vesicles of the rhombencephalon differentiate, a third flexure, the pontine flexure, develops between the mesencephalic and cervical flexures and demarcates the boundary between the metencephalon and myelencephalon.
•The folding of the rhombencephalon at the pontine flexures leads to the formation of the fourth ventricle.
Clinical Correlation Box 2.3: Congenital Hydrocephalus
Congenital hydrocephalus is a condition in which cerebrospinal fluid accumulates leading to dilation of the ventricular system. The most common cause of fluid accumulation is obstruction of CSF circulation that results from a narrowing (stenosis) of the cerebral aqueduct. This obstruction, called aqueductal stenosis, may occur during the formation of cerebral aqueduct within the mesencephalon.
Neural Tube Cellular Differentiation (Table 2.3) (Fig. 2.7a, b)
Table 2.3 Derivatives of neural tube wall: spinal cord and brainstem
Ventricular layer
Inner zone
Mantle layer
Intermediate zone
Marginal layer
Outer zone
Spinal cord
Immature neurons will migrate to form:
•Interneurons (relay)
•Projection neurons
•Somatic motor neurons
•Visceral motor neurons
Supportive neuroglial cells will migrate to form:
•Astrocytes
•Oligodendrocytes
•Radial glial
Ependymal cells line central canal
Gray matter
Neuron cell bodies associated with spinal nerves
Alar plate:
•Dorsal horn sensory nuclei
(interneurons)
Basal plate:
•Ventral horn somatic motor nuclei
•Lateral horn visceral motor neurons
White matter axonal tracts (fasciculi):
•Ascending
•Descending
•Commissures
Brainstem
Immature neurons:
•Interneurons
•Projection neurons
•Somatic motor neurons
•Visceral motor neurons
Supportive neuroglial cells will migrate to form:
•Astrocytes
•Oligodendrocytes
•Radial glial
Ependymal cells line fourth ventricle and choroid plexus
Gray matter
Neuron cell bodies associated with cranial nerves
•Alar plate—sensory nuclei
•Basal plate—motor nuclei
White matter axonal tracts (fasciculi):
•Ascending
•Descending
Commissures
•Neuroectoderm lining the lumen of the neural tube differentiates into three layers: an internal layer called the ventricular zone, an intermediate layer called the mantle zone, and an external layer called the marginal zone.
Fig. 2.7 (a,b) Cellular differentiation of neural tube. (a) Neuroectoderm forming the wall of the neural tube differentiates into three layers: an inner ventricular (ependymal) layer, a middle layer known as the mantle layer, and the outer marginal layer. (b) Each layer differentiates and gives rise to neuroglial cells, neuronal cell bodies of the gray matter, and the axons of the white matter. During development, neuroglial cells provide a structural scaffold that aids in the differentiation and migration of neurons to their final location. (Fig. 2.7a: Modified with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Second Edition, Vol 3. ©Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
•The neuroepithelial stem cells of the ventricular layer undergo rapid cell proliferation and give rise to neuroblasts (neurons), supportive neuroglial cells, and the ependymal cells of the choroid plexus.
•Following cellular proliferation in the ventricular layer, neurons migrate to their final destinations within the brain and spinal cord and eventually become organized in a laminar arrangement as the gray matter.
•Axons that differentiate from these neurons become organized into groups of ascending and descending tracts and form the white matter of the brain and spinal cord. Nerve fibers that cross the midline from one side of the brain or spinal cord to the other are referred to as commissures, and function to connect the two regions.
2.2 Spinal Cord Differentiation
2.2.1 Gray Matter: Alar and Basal Plate Development (Fig. 2.8a–c)
•In the spinal cord, neurons migrate from the ventricular zone and enter the mantle layer to form the gray matter. As neurons in the mantle zone grow, a longitudinal groove, known as the sulcus limitans, develops in the inner wall of the neural tube and divides the expanding mantle zone into dorsal and ventral regions. The neurons differentiating in the dorsal and ventral regions contribute to sensory (afferent) and motor (efferent) pathways, respectively, and become organized within the gray matter into functionally related groups of neurons known as nuclei and laminae.
Fig. 2.8 (a–c) Schematic pictures of the developing spinal cord cut in cross-section. (a,b) The developing neural tube differentiates into paired basal and alar plates, and an unpaired roof and floor plate. Neurons that originate in the mantle layer of the basal plate of the spinal cord become the efferent (motor) neurons, while neurons arising from the alar plate develop into interneurons that receive sensory input from the body. In the developing thoracolumbar and sacral regions, a paired intermediate plate develops and differentiates into efferent neurons associated with the autonomic nervous system (ANS). The outer marginal zone develops into white matter and contains afferent and efferent axonal fibers. (c) In the adult, the white matter aggregates to form three columns (funiculi), while the basal, intermediate, and alar plates differentiate into the gray matter of the ventral, lateral, and dorsal horns (columns), respectively. (Modified with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Second Edition, Vol 3. ©Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
•The dorsal region of the mantle zone is referred to as the alar plate, which eventually becomes the dorsal (posterior) horn of the spinal cord. The alar plate (dorsal horn) is comprised of sensory nuclei that receive sensory information from the periphery via nerve fibers that enter the spinal cord through the dorsal roots. The neurons developing from the alar plate form interneurons and projection neurons.
•The ventral region of the mantle zone is called the basal plate, which forms the ventral (anterior) horn of the spinal cord. The neurons of the basal plate (ventral horn) differentiate into somatic motor neurons that innervate skeletal muscle. Axons of the ventral horn neurons carry motor fibers and contribute to the ventral roots of spinal nerves.
•An additional group of neurons, which differentiate from an intermediate region between the alar and basal plates, will develop into the autonomic preganglionic visceral motor neurons located in the lateral horn of the spinal cord. These neurons are associated with the thoracolumbar (T1–L3) and sacral (S2–S4) segments of the spinal cord.
•Two thin cellular regions span the midline between the alar and basal plates, forming a roof plate and floor plate, respectively. The roof and floor plates serve to connect nerve fibers crossing from one side of the neural tube to the other. The floor plate contains the ventral white commissure.
2.2.2 White Matter (Fig. 2.9a, b)
•The white matter surrounds the gray matter in the spinal cord and brainstem.
Fig. 2.9 (a,b) Gray matter of the spinal cord. Three-dimensional representation of the spinal cord, oblique anterior view from the upper left. (a) Gray matter showing the location of the dorsal, lateral, and ventral horns (columns). Each column consists of clusters of functionally similar nuclei, which contains neurons associated with a specific function; interneurons of the dorsal horn receive somatic sensory input; the lateral horn contains autonomic motor neurons controlling visceral functions; the ventral horn consists of somatic motor neurons controlling voluntary motor function. (b) White matter surrounds the gray matter and consists of several functionally related axon tracts that are organized into three columns (funiculi). (Modified with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Second Edition, Vol 3. ©Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
•During development, axons from neurons in the alar and basal plates extend into the marginal zone and give rise to the white matter of the spinal cord. The nerve fibers of the white matter become organized into longitudinally arranged columns, referred to as funiculi. The funiculi consist of functionally related groups of axonal tracts (fasciculi) that transmit information to different levels of the spinal cord and brain. Typically, a group of tracts (fasciculi) travel together as the ascending and descending pathways that interconnect the spinal cord and brainstem to higher regions of the CNS.
•Axons originating from motor neurons in the ventral horn extend through the marginal layer and form motor fibers of the ventral root (Fig. 2.10a).
Fig. 2.10 (a,b) Schematic showing the development of a spinal nerve. (a) During early development, afferent (blue) and efferent (red) axons develop separately from neuron cell bodies and migrate along specific routes to their functional target. Arrows indicate the route of axonal migration. Neural crests cells migrate and develop into primary afferent (sensory) neurons found in the dorsal root (spinal) sensory ganglia. A central afferent process grows toward the central nervous system (CNS) and a peripheral afferent fiber extends toward developing body. Neural crest cells also give rise to autonomic neurons associated with autonomic ganglia (not shown in diagram). Somatic α-motor neurons (lower motor, ventral horn neurons) develop in the basal plate of the spinal cord. (b) Interneurons (black) develop from the alar plate and may form functional reflex connections between sensory and motor neurons or may receive and transmit sensory input to higher levels of the brain. The dorsal and ventral nerve roots represent the part of the peripheral nerve that connects the nerve to the spinal cord or brain. Efferent motor fibers of the ventral root join the afferent sensory fibers of the dorsal root distal to dorsal root ganglion to form peripheral spinal nerves. Spinal nerves emerging from the vertebral column represent mixed peripheral nerves that carry both efferent and afferent axons. There are 31 spinal nerves numbered according to their emergence from the vertebral canal. The C1–C7 nerve roots emerge above their respective vertebrae; the C8 nerve root emerges between the C7 and T1 vertebrae. The remaining nerve roots emerge below their respective vertebrae. (Modified with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Second Edition, Vol 3. ©Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
•Axons associated with neuron cell bodies located in the spinal sensory ganglia (dorsal root ganglia) form the primary sensory (afferent) nerve fibers of the dorsal root (Fig. 2.10b). The nerve fibers extend from peripheral sensory receptors and pass through dorsal root ganglia, to enter the dorsal horn, where the fibers may synapse on interneurons or ascend in the marginal layer (white matter) of the spinal cord to higher regions of the CNS.
•The motor fibers of the ventral root join with sensory nerve fibers of the dorsal root distal to the dorsal root ganglia to form a mixed spinal nerve (Fig. 2.10). The spinal nerves exit the developing vertebral column through the intervertebral foramina, an opening between adjacent vertebrae, and divide into dorsal and ventral rami.
2.2.3 Segmental Nerve Distribution: Myotomes and Dermatomes
•During development, the spinal cord exhibits a segmented pattern. The spinal cord gives rise to 31 pairs of spinal nerves that develop in association with bilateral swellings of mesodermal tissue known as somites (Fig. 2.11a, b).
Fig. 2.11 (a–c) Somite development and segmental nerve distribution (after Sadler). (a) Embryo at 22 days. Schematic illustrating eight pairs of somites flanking the partially closed neural tube along the dorsal surface. (b) Schematic cross-section taken at the plane of section shown in (a). (c) Schematic cross-section depicting segmented differentiation of paired somites. Paired somites, which represent specific body segments, extend from the midbrain to the caudal end of the spinal cord. Each pair of somites differentiates into a dermatome, myotome, and sclerotome segment, and directs the differentiation of the adjacent spinal nerve roots. As the paired somites and spinal nerve roots differentiate, a segmented arrangement of motor and sensory innervation becomes established. The segmented arrangement correlates with distinct innervation patterns associated with specific territories of the head, trunk, and extremities. The specific group of muscles that receives motor innervation from the same spinal motor root is known as a myotome. The area of skin transmitting cutaneous sensory input from a specific spinal sensory root is called a dermatome. (Modified with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Second Edition, Vol 1. © Thieme 2014. Illustrations by Markus Voll and Karl Wesker.)
•The paired somites, which represent body segments, extend from the midbrain to the caudal end of spinal cord. The somites establish a segmental pattern of motor and sensory innervation and direct the differentiation of adjacent spinal nerve roots.
•Each somite pair differentiates into three segments of tissue: a dermatome, a myotome, and a sclerotome, that gives rise to the dermis of the skin, skeletal muscle, and vertebrae, respectively. Each spinal nerve originating from a specific spinal cord segment innervates the associated region of muscle and skin that develops from a single specific somite (Fig. 2.11b).
•The groups of muscles that receive motor innervation from a single spinal nerve root are called myotomes, and the area of skin innervated by a single spinal sensory nerve root innervates is known as a dermatome. In the embryo, the motor and sensory innervation pattern exhibits an orderly arrangement, but due to the rotational growth of limbs, it becomes more complex in the adult (Fig. 2.12a,b).
Fig. 2.12 (a,b) Schematic representation of the embryonic and adult dermatome pattern. (a) A segmental pattern of innervation to the muscle (myotome) and skin (dermatomes) appears during embryonic development as each pair of spinal nerve roots differentiates along with an adjacent somite body segment. In the developing trunk, dermatomes are layered horizontally, and the corresponding nerve roots initially follow the outgrowth of the extremities. As the development continues, the limbs rotate around a longitudinal axis, which results in an oblique orientation of the dermatome pattern in the extremities. (b) In the adult, the dermatome pattern is slightly more complex than in the embryo. The dermatomes remain horizontally distributed in the trunk but follow a vertical pattern along the long axis of the limbs. In addition, the exact pattern may vary between individuals, and the innervation pattern may exhibit overlap between adjacent dermatomes. (Fig. 2.12a: Modified with permission from Kahle W, Frotscher M. Color Atlas of Human Anatomy, Sixth Edition, Vol 3. © Thieme 2011. Fig. 2.12b: Reproduced with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Second Edition, Vol 3. © Thieme 2016. Illustrations by Markus Voll and Karl Wesker.)
2.2.4 Positional Changes in Spinal Cord (Fig. 2.13a–c)
•During the first trimester, the spinal cord and surrounding vertebral column grow at similar rates. The spinal cord extends the entire length of the vertebral column and each spinal nerve emerges laterally from the vertebral column at their level of origin.
Fig. 2.13 (a–c) Positional change of the developing spinal cord within the vertebral column. During neonatal development, there is a rostral shift in the position of the spinal cord as a result of differential growth rates between the spinal cord and the vertebral column. (a) Third prenatal month. The spinal cord extends from the foramen magnum at the base of the skull throughout the length of the vertebral canal. The terminal part of the spinal cord, known as the conus medullaris, lies at the coccyx. (b) Rapid prenatal growth of the vertebral column causes a positional shift of the conus medullaris to ascend to the first lumbar (L1) vertebrae. (c) At the time of birth, the conus medullaris lies at the level of the L3 vertebra and is anchored to the vertebral column by the filum terminalis. In the adult, the conus medullaris lies at the L1 vertebral bodies and the spinal cord segments do not lie at the corresponding vertebral levels (not shown).
•As development proceeds, the growth rate of the vertebral column exceeds that of the spinal cord, such that at the time of birth the terminal part of the spinal cord, known as the conus medullaris, shifts to the third lumbar vertebrae (L3), and does not fill the vertebral column.
•The conus medullaris becomes anchored to the vertebral coccyx by a thin layer of specialized connective tissue known as the filum terminale.
•The space created within the vertebral column due to differential growth rates creates a dilation of the subarachnoid space known as the lumbar cistern.
•In the adult, the conus medullaris reaches the level between the first and second lumbar vertebrae. The spinal nerves emerging from the terminal segments of the spinal cord (L2–Co1) become elongated to form the cauda equina (horsetail) within the lumbar cistern. The spinal nerves of the cauda equina do not lie adjacent to their corresponding vertebral level and must descend within the lumbar cistern from their segment of origin to exit the corresponding vertebral level.
2.3 Brain Differentiation
2.3.1 Brainstem Differentiation
•The brainstem, comprised of the medulla, pons, and midbrain, exhibits a similar developmental pattern to that of the spinal cord.
○The neuroblasts migrate from the ventricular zone into the mantle layer and differentiate into nuclei associated with the sensory and motor columns of the alar and basal plates.
○The marginal layer of the brainstem comprises the white matter and consists of numerous ascending and descending tracts.
•Due to the expansion of the fourth ventricle, the nuclei of the alar plate migrate to the floor of the fourth ventricle and become located lateral to the motor neurons of the basal plate (Fig. 2.14a–c). This pattern continues throughout the brainstem, so that the sensory nuclei of the alar plate reside laterally, and the motor nuclei of the basal plate are medially located.
Fig. 2.14 (a–c) Brainstem development, migration of motor and sensory neurons, and establishment of cranial nerve nuclei (cross-sectional and cranial view of brainstem). (a) Early in embryonic development, the motor neurons reside in the ventral part of the brainstem (basal plate) and the sensory neurons lie in the dorsal part (alar plate). In the brainstem, the neurons of the alar and basal plate are associated with cranial nerves rather than spinal nerves. (b) As development continues and the fourth ventricle expands, the neurons in the alar plate migrate in a ventrolateral direction toward the floor of the fourth ventricle. Motor neurons of the basal plate remain ventral but migrate toward the midline. (c) The region of the medulla and pons from the rhombencephalon exhibit four nuclear columns that contain specific cranial nuclei. The somatomotor (lilac), visceromotor (orange and green stripes), viscerosensory (light blue), and somatosensory (dark blue) columns are indicated from medial to lateral. (after His and Herrick). (Modified with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Second Edition, Vol 1. © Thieme 2014. Illustrations by Markus Voll and Karl Wesker.)
•In the brainstem, the nuclei of alar and basal regions are associated with cranial nerves rather than spinal nerves. Cranial nerves provide a similar function as spinal nerves; however, some cranial nerves carry special sensory input for smell, sight, sound, and taste, while others provide innervation to muscles that function in speech, swallowing, and mastication (Fig. 2.15a, b).
Fig. 2.15 (a,b) Schematic diagrams illustrating cranial nerve development and position of cranial nerve nuclei in the adult. (a) (Sagittal view) Schematic of developing embryo at 6 weeks showing the relative position of the 12 cranial nerves and cervical spinal nerves (C1–C4). (b) (Left lateral view; mid-sagittal section) Relative position of the cranial nuclei and nerves in the adult. The cranial nerves are numbered and described according to their level of emergence from the brainstem. The level of emergence does not necessarily correspond to the location of the cranial nerve nuclei associated with the cranial nerve. (Modified with permission from Greenstein B, Greenstein A. Neuroanatomy and Neurophysiology. © Thieme 2000. Reproduced with permission from Baker EW. Anatomy for Dental Medicine. Second Edition. © Thieme 2015. Illustrations by Markus Voll and Karl Wesker.)
○Because of the functional and structural diversity in the head and neck region, cranial nerves exhibit a more complex pattern of sensory innervation.
○The cranial nerve nuclei of the alar and basal plates become organized into seven functional columns which reflect the functional requirements of the head and neck region. None of the cranial nerves carry all seven functional modalities (Fig. 2.16a–c) (Table 2.4).
Table 2.4 Origin of cranial nerve nuclei
Brainstem region
Forebrain region
Medulla
Pons
Midbrain
Diencephalon
Telencephalon
CN
CN IX Glossopharyngeal
CN X
Vagus
CN XI
Spinal Accessory
CNXII
Hypoglossal
CN V
Trigeminal
CN VI
Abducens
CN VII
Facial
CN VIII Vestibulocochlear
CN III
Oculomotor
CN VI
Trochlear
CN II
Optic
CN I
Olfactory
Fig. 2.16 (a–c) Arrangement of brainstem nuclear columns during embryonic development (after Herrick). Cross-sections through spinal cord and brainstem, superior view. The functional organization of the brainstem is determined by the location of the cranial nerve nuclei and corresponds to the pattern of neuron migration. (a) In the spinal cord, the motor neurons develop from the basal plate and lie in the ventral region of the cord. The sensory neurons of the spinal cord arise from the alar plate and reside in the dorsal region of the cord. (b) Early embryonic view of the brainstem (arrows indicate the migration path). In the brainstem, the cranial nerves of the alar and basal plate become organized into seven functional columns that reflect the functional requirements of the head. Sensory neurons of the alar plate migrate laterally to form sensory nuclei, while motor neurons of the basal plate migrate medially to form the motor nuclei. This results in a general mediolateral arrangement of the neurons into specific nuclear columns. (c) Cross-section through the medulla. The adult brainstem features a medial to lateral arrangement of four longitudinal columns of nuclei. In each column, the nuclei which have the same function are arranged in a craniocaudal pattern. The nuclei in the somatic afferent and visceral afferent column differentiate into general somatic (GSA) nuclei, general visceral afferent (GVA) nuclei, and special sensory afferent (SVA) nuclei. Similarly, the visceral efferent nuclear column differentiates into general visceral efferent (GVE) (parasympathetic) nuclei and special visceral efferent (SVE) (branchiomeric) nuclei. SVE nuclei develop in association with the skeletal muscles of the head that arise from the pharyngeal arches. In the region of the medulla, general somatic nuclei correspond to the motor nuclei of the CN XII (hypoglossal nerve). (Reproduced with permission from Schuenke M, Schulte E, Schumacher U. THIEME Atlas of Anatomy Third Edition, Vol 3. © Thieme 2020. Illustrations by Markus Voll and Karl Wesker.)
•CN I and II develop from the forebrain, while the cranial nerve nuclei associated with CN III through XII, originate from the brainstem.
2.3.2 Forebrain and Cerebellar Differentiation (Table 2.5)
Table 2.5 Derivatives of neural tube wall: cerebellum and forebrain
Ventricular layer
Inner zone
Mantle layer
Intermediate zone
Marginal layer
Outer zone
Cerebellum
Immature neurons migrate to form:
•Interneurons
○Basket cells
○Stellate cells
•Projection neurons
•Purkinje cells
•Granular cells
•Deep cerebellar neurons
Supportive neuroglial cells migrate to form
•Astrocytes
•Oligodendrocytes
•Radial glial
Ependymal cells line third ventricles and choroid plexus
White matter:
Axonal tracts form the
•Cerebellar peduncles
Gray matter:
•Deep cerebellar nuclei
Gray matter:
Cerebellar cortex:
Three layers:
•Molecular layer
•Purkinje layer
•Granular layer
Forebrain
Cerebral hemispheres
Diencephalon
Immature neurons:
•Interneurons
•Projection neurons
•Pyramidal cells
•Golgi I and II cells
Supportive neuroglial cells:
•Astrocytes
•Oligodendrocytes
•Radial glial
Ependymal cells line lateral ventricles and choroid plexus
White matter:
Axonal tracts:
•Ascending
•Descending
•Commissures
Gray matter:
•Basal ganglia nuclei
○Corpus striatum (cerebral hemispheres)
○Subthalamic nuclei (diencephalon)
○Substantia nigra (midbrain)
Gray matter:
•Laminar arrangement of cortical neurons
•Rostral to the brainstem, differentiation of the developing neural tube is more complex and is modified to accommodate the development of the cerebellar and cerebral cortices.
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