Neural - Spinal Cord Development

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Stage10 sem6.jpg

Introduction

Neural groove closing to neural tube
Embryo early week 4 (Stage 10)
Spinal cord transverse section week 8
Spinal cord transverse section
Embryo week 8 (Carnegie Stage 22)

The spinal cord is the central nervous system part that extends into the axial skeleton and provides the two-way traffic required to interact with our environment. During pregnancy, early development of the spinal cord is influenced by the maternal dietary requirement for folate for closure of the neural tube. Later development requires the contribution of neural crest associating with the cord to form the dorsal root ganglia and ventral sympathetic ganglia. The animal models of spinal cord development has also been a key models of patterning, establishing ventral and dorsal compartments based upon surrounding signals.


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).


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.


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.


Neural Links: neural | ventricular | ectoderm | Stage 22 | gliogenesis | neural fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | neural crest | Sensory | neural abnormalities | folic acid | iodine deficiency | Fetal Alcohol Syndrome | Postnatal | 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

  • Species-specific Posture of Human Foetus in Late First Trimester[1] The ontogeny associated with the arm-hanging posture, which is considered ape-specific, remains unknown. To examine its ontogeny, we measured foetal movements of 62 human foetuses aged 10-20 gestation weeks using four-dimensional sonography. We observed that the first-trimester foetuses show this particular species-specific posture. After 11 weeks of gestation, all foetuses showed the arm-hanging posture, and the posture was most frequently observed at 14-16 weeks of gestation. Moreover, this posture often involved extension of both arms and both legs, indicating that it is not myogenic but neurogenic. Furthermore, early ontogeny suggests that it originates because of subcortical activity. Such posture extension bias and persistence indicates that vestibulospinal tract maturation involves the ontogeny of arm-hanging posture during 14-16 weeks of gestation." limb
  • Review - The Multiple Roles of FGF Signaling in the Developing Spinal Cord[2] "During vertebrate embryonic development, the spinal cord is formed by the neural derivatives of a neuromesodermal population that is specified at early stages of development and which develops in concert with the caudal regression of the primitive streak. Several processes related to spinal cord specification and maturation are coupled to this caudal extension including neurogenesis, ventral patterning and neural crest specification and all of them seem to be crucially regulated by Fibroblast Growth Factor (FGF) signaling, which is prominently active in the neuromesodermal region and transiently in its derivatives. Here we review the role of FGF signaling in those processes, trying to separate its different functions and highlighting the interactions with other signaling pathways." FGF
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Spinal Cord Embryology

Jelena Tosic, Zeljka Stanojevic, Sasenka Vidicevic, Aleksandra Isakovic, Darko Ciric, Tamara Martinovic, Tamara Kravic-Stevovic, Vladimir Bumbasirevic, Verica Paunovic, Svetlana Jovanovic, Biljana Todorovic-Markovic, Zoran Markovic, Martin Danko, Matej Micusik, Zdenko Spitalsky, Vladimir Trajkovic Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats. Neuropharmacology: 2018; PubMed 30471296

Eleni Triantafyllidi, Alexandra Papoudou-Bai, George A Alexiou, Anastasia Zikou, Antonia Charchanti, Nikolaos Konsolakis, Dionysoula Skiada, Spyridon Voulgaris, Anna C Goussia Adult intradural extramedullary teratoma of the spinal cord: A case presentation. Clin Neurol Neurosurg: 2018, 175;54-56 PubMed 30384116

Rania A Galhom, Hoda H Hussein Abd El Raouf, Mona H Mohammed Ali Role of bone marrow derived mesenchymal stromal cells and Schwann-like cells transplantation on spinal cord injury in adult male albino rats. Biomed. Pharmacother.: 2018, 108;1365-1375 PubMed 30372839

Luyao Xu, Benson O A Botchway, Songou Zhang, Jingying Zhou, Xuehong Liu Inhibition of NF-κB Signaling Pathway by Resveratrol Improves Spinal Cord Injury. Front Neurosci: 2018, 12;690 PubMed 30337851

Halil Ibrahim Suner, Gokhan Kurt, Zuhal Yildirim, Erkut Baha Bulduk, Alp Ozgun Borcek, Harun Demirci, Bahar Kartal, Gulnur Take Kaplanoglu Investigation Of The Effect Of Alemtuzumab In An Experimental Spinal Cord Trauma Model In Rats. World Neurosurg: 2018; PubMed 30292667

Older papers  
  • Coordination of progenitor specification and growth in mouse and chick spinal cord[3] "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[4] "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[5]

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

Brain
Prosencephalon Telencephalon Rhinencephalon, Amygdala, Hippocampus, Cerebrum (Cortex), Hypothalamus, Pituitary | Basal Ganglia, lateral ventricles
Diencephalon Epithalamus, Thalamus, Subthalamus, Pineal, third ventricle
Mesencephalon Mesencephalon Tectum, Cerebral peduncle, Pretectum, cerebral aqueduct
Rhombencephalon Metencephalon Pons, Cerebellum
Myelencephalon Medulla Oblongata
Spinal Cord

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.[6]

  • 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).[7][8]
  • 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

 ‎‎Mobile | Desktop | Original

Stage 22 | Embryo Slides
These listed features link to zoomed views of the virtual slide with the named feature generally in the centre of the view.

Use the (-) at the top left of the screen to see where this feature is located.

Spinal Cord Features Other Features

Fetal Development

Links: fetal

Conus Medullaris

Human week 10 fetus
Conus Medullaris (week 10, GA week 12)

The conus medullaris (Latin, "medullary cone") is the tapered, lower end of the spinal cord. An ultrasound study of the position of the spinal cord conus medullaris at 18-22 weeks (20 to 24 weeks ((GA}}) showed that it ended adjacent to vertebrae L2, L2-3 vertebral space, and L3 (73/78, 93%).[9]


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[10]

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>

Abnormalities

Spinal Muscular Atrophy

ICD-11 8B61 Spinal muscular atrophy (ICD-10-CM Diagnosis Code G12.9)

Spinal muscular atrophy (SMA) is a rare neural autosomal recessive genetic condition that leads to a loss of motor neurons and then progressive muscle wasting. A new drug treatment using nusinersen[11] (trade name Spinraza®), see reviews[12][13], has led to the recent inclusion of SMA in the newborn heel-prick test (Guthrie test). Clinical classification of SMA type depends upon the age of onset and highest level of motor function achieved.


This genetic disease exists in several different forms related to SMN1 gene on chromosome 5q13:
  • Type 1 - caused by mutation or deletion in the telomeric copy of the SMN1 gene.
  • Type 2 - caused by homozygous or compound heterozygous mutation in the SMN1 gene.
  • Type 3 - caused by homozygous or compound heterozygous mutation in the SMN1 gene.


SMN1 - (5q13) encodes a 38 kD protein expressed in neuronal cytoplasm and nucleus. Nuclear SMN is located in Cajal bodies ("GEMS", Gemini of the coiled bodies; nucleolar accessory bodies; coiled body) involved in mRNA metabolism. These are proposed sites where small nuclear ribonucleoproteins (snRNPs) and small nucleolar RNAs (snoRNPs) are modified. Cajal bodies were first reported in 1903 by the Spanish cytologist/histologist Cajal, who christened them "nucleolar accessory bodies".

Cajal bodies
Cajal bodies panel (D) EM purified CB, SMN (arrowheads).[14]

The Hammersmith Functional Motor Scale (HFMS), was first developed in 2003 and recently revised by international collaboration[15] as a tool for assessment of the physical abilities of SMA type 2 and type 3 patients with limited ambulation. (More? Hammersmith Functional Motor Scale - 2015 revision)


Links: skeletal muscle | Search PubMed Spinal muscular atrophy


References

  1. Ohmura Y, Morokuma S, Kato K & Kuniyoshi Y. (2018). Species-specific Posture of Human Foetus in Late First Trimester. Sci Rep , 8, 27. PMID: 29311655 DOI.
  2. Diez Del Corral R & Morales AV. (2017). The Multiple Roles of FGF Signaling in the Developing Spinal Cord. Front Cell Dev Biol , 5, 58. PMID: 28626748 DOI.
  3. Kicheva A, Bollenbach T, Ribeiro A, Valle HP, Lovell-Badge R, Episkopou V & Briscoe J. (2014). Coordination of progenitor specification and growth in mouse and chick spinal cord. Science , 345, 1254927. PMID: 25258086 DOI.
  4. Demireva EY, Shapiro LS, Jessell TM & Zampieri N. (2011). Motor neuron position and topographic order imposed by β- and γ-catenin activities. Cell , 147, 641-52. PMID: 22036570 DOI.
  5. Pyrgaki C, Trainor P, Hadjantonakis AK & Niswander L. (2010). Dynamic imaging of mammalian neural tube closure. Dev. Biol. , 344, 941-7. PMID: 20558153 DOI.
  6. Wilson L & Maden M. (2005). The mechanisms of dorsoventral patterning in the vertebrate neural tube. Dev. Biol. , 282, 1-13. PMID: 15936325 DOI.
  7. Chizhikov VV & Millen KJ. (2004). Mechanisms of roof plate formation in the vertebrate CNS. Nat. Rev. Neurosci. , 5, 808-12. PMID: 15378040 DOI.
  8. Chizhikov VV & Millen KJ. (2005). Roof plate-dependent patterning of the vertebrate dorsal central nervous system. Dev. Biol. , 277, 287-95. PMID: 15617675 DOI.
  9. Perlitz Y, Izhaki I & Ben-Ami M. (2010). Sonographic evaluation of the fetal conus medullaris at 20 to 24 weeks' gestation. Prenat. Diagn. , 30, 862-4. PMID: 20582935 DOI.
  10. Zannino DA & Sagerström CG. (2015). An emerging role for prdm family genes in dorsoventral patterning of the vertebrate nervous system. Neural Dev , 10, 24. PMID: 26499851 DOI.
  11. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W & De Vivo DC. (2017). Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N. Engl. J. Med. , 377, 1723-1732. PMID: 29091570 DOI.
  12. Gidaro T & Servais L. (2018). Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps. Dev Med Child Neurol , , . PMID: 30221755 DOI.
  13. Vukovic S, McAdam L, Zlotnik-Shaul R & Amin R. (2018). Putting our best foot forward: Clinical, treatment-based and ethical considerations of nusinersen therapy in Canada for spinal muscular atrophy. J Paediatr Child Health , , . PMID: 30246272 DOI.
  14. Ogg SC & Lamond AI. (2002). Cajal bodies and coilin--moving towards function. J. Cell Biol. , 159, 17-21. PMID: 12379800 DOI.
  15. Ramsey D, Scoto M, Mayhew A, Main M, Mazzone ES, Montes J, de Sanctis R, Dunaway Young S, Salazar R, Glanzman AM, Pasternak A, Quigley J, Mirek E, Duong T, Gee R, Civitello M, Tennekoon G, Pane M, Pera MC, Bushby K, Day J, Darras BT, De Vivo D, Finkel R, Mercuri E & Muntoni F. (2017). Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool. PLoS ONE , 12, e0172346. PMID: 28222119 DOI.

Reviews

Greene ND & Copp AJ. (2009). Development of the vertebrate central nervous system: formation of the neural tube. Prenat. Diagn. , 29, 303-11. PMID: 19206138 DOI.

Ulloa F & Martí E. (2010). Wnt won the war: antagonistic role of Wnt over Shh controls dorso-ventral patterning of the vertebrate neural tube. Dev. Dyn. , 239, 69-76. PMID: 19681160 DOI.

Dasen JS & Jessell TM. (2009). Hox networks and the origins of motor neuron diversity. Curr. Top. Dev. Biol. , 88, 169-200. PMID: 19651305 DOI.

Dessaud E, McMahon AP & Briscoe J. (2008). Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network. Development , 135, 2489-503. PMID: 18621990 DOI.

Molyneaux BJ, Arlotta P & Macklis JD. (2007). Molecular development of corticospinal motor neuron circuitry. Novartis Found. Symp. , 288, 3-15; discussion 15-20, 96-8. PMID: 18494249

Glenn OA & Barkovich AJ. (2006). Magnetic resonance imaging of the fetal brain and spine: an increasingly important tool in prenatal diagnosis, part 1. AJNR Am J Neuroradiol , 27, 1604-11. PMID: 16971596

Glenn OA & Barkovich J. (2006). Magnetic resonance imaging of the fetal brain and spine: an increasingly important tool in prenatal diagnosis: part 2. AJNR Am J Neuroradiol , 27, 1807-14. PMID: 17032846

Sadler TW. (2005). Embryology of neural tube development. Am J Med Genet C Semin Med Genet , 135C, 2-8. PMID: 15806586 DOI.

Placzek M & Briscoe J. (2005). The floor plate: multiple cells, multiple signals. Nat. Rev. Neurosci. , 6, 230-40. PMID: 15738958 DOI.

Articles

Saitsu H & Shiota K. (2008). Involvement of the axially condensed tail bud mesenchyme in normal and abnormal human posterior neural tube development. Congenit Anom (Kyoto) , 48, 1-6. PMID: 18230116 DOI.

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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Historic

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Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)
Filum Terminale (1919)
Streeter GL. Factors involved in the formation of the filum terminale. (1919) Amer. J Anat. 22:1-11.
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.


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