Early Development of Neural Tube Development of Medulla Spinalis and Peripheral Nervous System. Assoc.Prof. E.Elif Güzel, M.D.

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1 Early Development of Neural Tube Development of Medulla Spinalis and Peripheral Nervous System Assoc.Prof. E.Elif Güzel, M.D.

2 Third week of Embryogenesis Primitive streak/pit appears on the epiblast (day 15) 3 germ layers differentiate (gastrulation) Embryonic ectoderm Intraembryonic mesoderm Embryonic endoderm

3 Formation of the Neural Plate In the 3rd week, developing notochord and the paraxial mesoderm induces overlying ectoderm (cranial to the primitive streak) to become neuroectoderm. The elongated, slipper-shaped plate of thickened ectoderm is called the neural plate (day 18). Inducing signaling molecules are the members of TGF-β family (Shh and BMPs).

4 Neural plate invaginates- neural groove, lateral edges elevates- neural folds (day 20)

5 Neurulation (Formation of the neural tube) Neural groove invaginates and neural folds approach each other and fuse to form the neural tube (day 22). Fusion begins in the cervical region (4-6 somite level) and proceeds in cephalic and caudal directions. Cephalic region -future brain, caudal region -future spinal cord. Neural tube detaches from the surface ectoderm which will form the epidermis.

6 There are 2 parts where the neural tube is still open and in communication with the amniotic cavity: Cranial neuropore Caudal neuropore These opened parts will close at 25th 27th day

7 As the neural plate invaginates, ectodermal neural crest cells appear at the border. As the neural tube detaches from the surface ectoderm neural crest cells fuse, undergo into mesenchymal transition, and remain between the surface ectoderm and the neural tube. Neural crest cells migrate through the periphery and differentiate into many cell types.

8 Derivatives of neural tube Brain Spinal cord Neurons and supporting cells of the CNS Somatomotor neurons of the PNS Presynaptic autonomic neurons of PNS

9 Derivatives of the neural crest Sensory neurons in the PNS Postsynaptic autonomic neurons Schwann cells Arachnoid and piamater of meninges Odontoblasts Adrenal medulla cells Head mesenchyme Melanocytes in the skin

10 Development of medulla spinalis The neural tube caudal to the 4 th pair of somites develops into the spinal cord. The walls of the neural tube thicken. Size of the neural canal gradually reduces and persists as central canal at week 10.

11 Cytodifferentiation of the neural tube The wall of the recently closed neural tube- neuroepithelial cells (pseudostratified ep.) Neuroepithelial cells divide neuroblasts form the mantle zone (around the neuroepithelial layer)

12 After neuroblast formation stops, the neuroepithelium gives rise to glioblasts which migrate to mantle and marginal zones. When the neuroepithelial cells cease producing neuroblasts and glioblasts, they differentiate into ependymal cells. Microglial cells are mesenchymal, they invade the CNS in fetal period with the blood vessels.

13 Various stages of development of a neuroblast

14 Neural tube is composed of 3 layers; 1. Ventricular (ependymal) layer innermost cells lining the lumen 2. Mantle layer (gray matter) the neuroblasts migrated from the neuroepithelium future gray matter of the spinal cord 3. Marginal layer outermost processes of cells in the mantle zone future white matter of the spinal cord

15 Proliferation and differentiation of neuroepithelial cells in the developing spinal cord produce thick walls and thin roof-, floor- plate. Differential thickening of the lateral walls produces longitudinal groove on each side- sulcus limitans. Alar plate forms the dorsal horn of the gray matter Basal plate forms the ventral horn of the gray matter Sulcus limitans seperates the alar plate from the basal plate.

16 The ventral root of the spinal nerve is composed of nerve fibers arising from neuroblasts in the basal plate, whereas the dorsal root is formed by nerve processes arising from neuroblasts in the spinal ganglion.

17 Development of the spinal ganglia Neural crest cells differentiate into pseudounipolar neurons satellite cells

18 Development of meninges Develop from cells of the neural crest and mesenchyme (days 20-35) Primordial meninges External dura mater Internal pia arachnoid (leptomeninges) Fluid filled spaces occur between leptomeninges and form the subarachnoid space Leptomeninges subdivides into pia mater and arachnoid mater

19 Positional changes of spinal cord (SC) Firstly, SC extends the entire length of the vertebral canal and spinal nerves (SN) pass through the intervertebral foramina at the levels of their origin. Vertebral column (VC) and dura mater grow more rapidly than the SC, the caudal end of the SC gradually comes to lie at relatively higher levels. The SN run obliquely from the SC to the corresponding level of the VC. In adults SC ends; L2-L3, dura- and arachnoid-mater end; S2. Pia mater, passes through the dura and attaches to the periosteum of the 1 st coccygeal vertebra (filum terminale) (indicates the original level of the end of spinal cord).

20 Myelination of nerve fibers Myelin sheaths begin to form during the late fetal period and continue to form during the first postnatal year. Oligodendrocytes originate from neuroepithelium. Schwann cells originate from neural crest cells.

21 Development of PNS All sensory cells of PNS (e.g. dorsal root ganglia, trigeminal ganglia) are derived from neural crest cells. Peripheral sensory cells are at first bipolar, then they differentiate into unipolar cells (except the sensory cells in the ganglion of CN VIII) Multipolar cells in the autonomic ganglia derives from neural crest cells. Satellite cells derives from neural crest cells. The connective tissue around the ganglion cells are derived from mesenchyme.

22 Development of spinal nerves As the limb buds grow, the axons from spinal cord segments (multipolar neurons derived from basal plate) elongate and grow into the limb (end of 4 th week). Sensory neurons give extensions to form spinal nerves as well. Connective tissue sheaths of the peripheral nerves are derived from mesenchyme.

23 References 1. The Developing Human: Clinically Oriented Embryology by Keith L. Moore, T. V. N. Persaud and Mark G. Torchia (2013). 9 th ed. Elsevier Saunders, Philadelphia. ISBN: Langman s Medical Embryology by T.W. Sadler (2012). 12 th ed. Lippincott Williams & Wilkins, Philadelphia. ISBN: Human Embryology by Larsen WJ (2001). 3rd ed. Churchill Livingstone, Philadelphia. ISBN: Netter s Atlas of Human Embryology by Larry R. Cochard (2002). 1 st ed. Icon Learning Systems, New Jersey. ISBN:

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