Neural - Spinal Cord Development

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Stage10 sem6.jpg

Introduction

Neural groove closing to neural tube, early week 4
(Stage 10)

Neural development is one of the earliest systems to begin and the last to be completed after birth. This development generates the most complex structure within the embryo and the long time period of development means in utero insult during pregnancy may have consequences to development of the nervous system.

The early central nervous system begins as a simple neural plate that folds to form a groove then tube, open initially at each end. Failure of these opening to close contributes a major class of neural abnormalities (neural tube defects).

Within the neural tube stem cells generate the 2 major classes of cells that make the majority of the nervous system : neurons and glia. Both these classes of cells differentiate into many different types generated with highly specialized functions and shapes. This section covers the establishment of neural populations, the inductive influences of surrounding tissues and the sequential generation of neurons establishing the layered structure seen in the brain and spinal cord.

  • Neural development beginnings quite early, therefore also look at notes covering Week 3- neural tube and Week 4-early nervous system.
  • Development of the neural crest and sensory systems (hearing/vision/smell) are only introduced in these notes and are covered in other notes sections.


Neural Links: ectoderm | neural | neural crest | ventricular | sensory | Stage 22 | gliogenesis | neural fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | neural abnormalities | folic acid | iodine deficiency | Fetal Alcohol Syndrome | neural postnatal | neural examination | Histology | Historic Neural | Category:Neural
Human embryo (Carnegie stage 13) spinal cord (shown in cross-section at the bottom of image).

Some Recent Findings

  • Coordination of progenitor specification and growth in mouse and chick spinal cord[1] "Our data show that domain proportions are first established by opposing morphogen gradients and subsequently controlled by domain-specific regulation of differentiation rate but not differences in proliferation rate. Regulation of differentiation rate is key to maintaining domain proportions while accommodating both intra- and interspecies variations in size. Thus, the sequential control of progenitor specification and differentiation elaborates pattern without requiring that signaling gradients grow as tissues expand."
  • Motor neuron position and topographic order imposed by β- and γ-catenin activities[2] "Neurons typically settle at positions that match the location of their synaptic targets, creating topographic maps. In the spinal cord, the organization of motor neurons into discrete clusters is linked to the location of their muscle targets, establishing a topographic map of punctate design. To define the significance of motor pool organization for neuromuscular map formation, we assessed the role of cadherin-catenin signaling in motor neuron positioning and limb muscle innervation. We find that joint inactivation of β- and γ-catenin scrambles motor neuron settling position in the spinal cord but fails to erode the predictive link between motor neuron transcriptional identity and muscle target. Inactivation of N-cadherin perturbs pool positioning in similar ways, albeit with reduced penetrance. These findings reveal that cadherin-catenin signaling directs motor pool patterning and imposes topographic order on an underlying identity-based neural map."
  • Dynamic imaging of mammalian neural tube closure[3]
More recent papers
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Search term: Spinal Cord Embryology

<pubmed limit=5>Spinal Cord Embryology</pubmed>

Neural Development Overview

Neuralation begins at the trilaminar embryo with formation of the notochord and somites, both of which underly the ectoderm and do not contribute to the nervous system, but are involved with patterning its initial formation. The central portion of the ectoderm then forms the neural plate that folds to form the neural tube, that will eventually form the entire central nervous system.

Early developmental sequence: Epiblast - Ectoderm - Neural Plate - Neural groove and Neural Crest - Neural Tube and Neural Crest


Neural Tube Development
Neural Tube Primary Vesicles Secondary Vesicles Adult Structures
week 3 week 4 week 5 adult
neural plate
neural groove
neural tube

Brain
prosencephalon (forebrain) telencephalon Rhinencephalon, Amygdala, hippocampus, cerebrum (cortex), hypothalamus‎, pituitary | Basal Ganglia, lateral ventricles
diencephalon epithalamus, thalamus, Subthalamus, pineal, posterior commissure, pretectum, third ventricle
mesencephalon (midbrain) mesencephalon tectum, Cerebral peduncle, cerebral aqueduct, pons
rhombencephalon (hindbrain) metencephalon cerebellum
myelencephalon medulla oblongata, isthmus
spinal cord, pyramidal decussation, central canal

Early Brain Vesicles

In week 3, the neural plate forms and the caudal end of the neural plate remains narrow compared to the cranial end which rapidly expands.

In week 4, when the plate folds to form the neural tube, the cranial end of the tube then forms a series of enlarged cavities (vesicles) that will eventually form the brain. The caudal end of the tube forms a narrower tube of relatively the same size along its length that will eventually form the spinal cord.

Primary Vesicles Secondary Vesicles
CNS primary vesicles.jpg CNS secondary vesicles.jpg
early embryonic late embryonic

Human brain growth 01.jpg

Direct comparison of brain growth embryonic and fetal period. Note the relative size of the spinal cord seen at the lower end of each image.

Spinal Cord Regions

The neural tube forms similar regions around the wall along its length, including the spinal cord. The floor and roof plate are specialised developmental regions, important embryonic "patterning" regions.[4]

  • Floor plate - thin wall region that overlies the notochord. Ventral patterns the spinal cord, both floor plate and notochord produce Sonic hedgehog (Shh) (see also Notochord)
  • Basal plate - thick wall region lying either side of the floor floor plate. The ventral horn motor neurons develop here and extend axons out of the spinal cord to innervate developing skeletal muscle. Tracts formed by axons surround these horns and project both up and down the spinal cord.
  • Alar plate - thick wall region lying either side of the roof floor plate. The sensory dorsal horn develops there and receives axons from the sensory structures outside the spinal cord. The adult horn is divided into 6 laminae (I to VI). Tracts formed by axons surround these horns and project both up and down the spinal cord.
  • Roof plate - thin wall region that underlies the dorsal ectoderm epithelium. Dorsal patterns the spinal cord, the roof plate produces Bone morphogenetic proteins (BMPs). [5][6]
  • Lumen - neuroepithelium lined fluid-filled space continuous with the brain ventricular system.
Week 4 Week 8
Stage13 spinal cord02.jpg Human Stage22 spinal cord02.jpg
Stage 13 Spinal cord cross-section (upper part of cord).
labeled image | unlabeled image
Stage 22 Spinal cord cross-section (ventral is at bottom of image)
labeled image | unlabeled image

Embryonic Development

Week 4

Spinal cord cross-section (upper part of cord) (Carnegie Stage 13)
Stage13 spinal cord01.jpg Stage13 spinal cord02.jpg

Week 8

Human Stage22 spinal cord02.jpg

Virtual Slide

Stage 22 - Spinal Cord (rotated)

Human Stage22 spinal cord03.jpg

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Stage 22 | Embryo Slides
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Spinal Cord Features Other Features

Plexus Development

The spinal nerves initially leave the spinal cord at each individual segmental levels. At various levels they then form an intersecting network of nerves, a plexus, from which mixed segmental nerves emerge.


Cervical Plexus

Adult Cervical Plexus
Gray0804.jpg

(plexus cervicalis)

  • formed by the anterior divisions of the upper four cervical nerves
  • each nerve, except the 1st, divides into an upper and a lower branch, and the branches unite to form three loops.
  • branches are divided into two groups, superficial and deep.

Search PubMed: cervical plexus embryology

Brachial Plexus

Adult Brachial Plexus
Gray0807.jpg

plexus brachial

  • plexus extends from the lower part of the side of the neck to the axilla.
  • nerves that form it are similar in size, mode of communication is subject to some variation.
  • formed by union of the anterior divisions of the lower 4 cervical nerves and the greater part of the anterior division of the first thoracic nerve.
  • 4th cervical usually gives a branch to the 5th cervical.
  • 1st thoracic frequently receives one from the 2nd thoracic.
Search PubMed: brachial plexus embryology

Lumbar Plexus

Adult Lumbar Plexus
Gray0822.jpg

plexus lumbalis

  • formed by anterior divisions of the first three and the greater part of the 4th lumbar nerves.
  • 1st lumbar often receives a branch from the last thoracic nerve.
Search PubMed: lumbar plexus embryology

Sacral Plexus

Dermatomes

A dermatome represents the area of skin that is mainly supplied by a single spinal nerve. Therefore each spinal nerve can be "mapped" to a region of the external body surface and that this "map" is established before embryonic limb rotation.


Links: Sensory - Touch Development | Limb Development

Molecular

Neural tube dorsoventral patterning SHH BMP.jpg|

Neural tube Dorsoventral Patterning by SHH BMP[7]

Dorsoventral domains are established by opposing concentration gradients of Sonic Hedgehog (Shh) and Bone Morphogenic Protein (BMP).

  • left - These regulate progenitor gene expression. The progenitor genes cross-repress each other to establish domain boundaries.
  • right - Each domain will give rise to a specific cell type that expresses various post-mitotic differentiation genes.


Links: SHH | BMP

Spinal Cord Histology

Identify gray and white matter, central canal (surrounded by ependymal cells), dorsal and ventral horns, meninges (pia, arachnoid and dura mater), subarachnoid space with dorsal and ventral rootlets, blood vessels, a motor neurone with a cell body (soma), nucleus, nucleolus, Nissl granules, an axon with axon hillock area, dendrites, glial cells (oligodendrocytes, astrocytes).

Spinal cord (Luxol Fast Blue)
Spinal cord histology 01.jpg Spinal cord histology 02.jpg
Spinal cord - Grey and white matter
Spinal cord histology 03.jpg Spinal cord histology 04.jpg
Spinal cord - Grey matter
Spinal cord histology 11.jpg

Grey matter (HE)

Spinal cord histology 12.jpg

Grey matter (silver)

Spinal Cord: Overview 1 | Overview 2 | Overview animation | Grey matter | Grey matter | Grey matter | White matter | Overview unlabeled | Grey matter unlabeled 1 | Grey matter unlabeled 2 | White matter unlabeled 1 | Ependymal cells unlabeled


Spinal cord histology 10.jpg
Mouse ependymal cilia 01-icon.jpg
 ‎‎Ependymal cilia
Page | Play
<mediaplayer width='600' height='230' image="http://php.med.unsw.edu.au/embryology/images/5/5f/Mouse_ependymal_cilia_01-icon.jpg">File:Mouse_ependymal_cilia_01.mp4</mediaplayer>


Additional Images

Historic

Human Embryology And Morphology (1921)
Keith, A. Human Embryology And Morphology (1921) Longmans, Green & Co.:New York.

7 Spinal Cord

Anatomy of the Human Body (1918)
Gray, H. Anatomy of the Human Body. Philadelphia: Lea & Febiger, 1918.

References

  1. <pubmed>25258086</pubmed>
  2. <pubmed>22036570</pubmed>
  3. <pubmed>20558153</pubmed>
  4. <pubmed>15936325</pubmed>
  5. <pubmed>15378040</pubmed>
  6. <pubmed>15617675</pubmed>
  7. 26499851</pubmed>| Neural Dev.

Reviews

<pubmed>19206138</pubmed> <pubmed>19681160</pubmed> <pubmed>19651305</pubmed> <pubmed>18621990</pubmed> <pubmed>18494249</pubmed> <pubmed>16971596</pubmed> <pubmed>17032846</pubmed> <pubmed>15806586</pubmed> <pubmed>15738958</pubmed>

Articles

<pubmed>18230116</pubmed>

Books

Search PubMed

November 2010 search "Spinal Cord Embryology" All (7631) Review (641) Free Full Text (1562)

Search Pubmed: Spinal Cord Embryology | Spinal Cord Development



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