1. DEVELOPMENT OF CNS Dr. Lubna Nazli 1

2. Objectives Development of neural tube, its divisions and derivatives. Histogenesis of neural tube Development of meninges Developmental anomalies 2

3. Formation of neural tube – At the beginning of the third week of development, the ectodermal germ layer has the shape of a disc that is broader in the cephalic than the caudal region. 3

4. Appearance of the notochord induces the overlying ectoderm to thicken and form the neural plate. 4

5. By the end of the third week, the lateral edges of the neural plate become more elevated to form neural folds, and the depressed mid region forms the neural groove 5

6. Gradually, the neural folds approach each other in the midline, where they fuse. 6

7. – cells along the margin of the neural groove are called the neural crest cells. develop into sensory and sympathetic neurons and schwann cells 7

8. Fusion begins in the cervical region and proceeds cranially and caudally. As a result, the neural tube is formed. Until fusion is complete, the cephalic and caudal ends of the neural tube communicate with the amniotic cavity by way of the cranial and caudal neuropores, respectively 8

9. Neurulation is then complete, and the central nervous system is represented by a closed tubular structure with a narrow caudal portion, the spinal cord, and a much broader cephalic portion characterized by a number of dilations, the brain vesicles 9

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11. Neural Tube Histogenesis 11

12. The wall of a recently closed neural tube consists of neuroepithelial cells. These cells extend over the entire thickness of the wall and form a thick pseudostratified epithelium. Immediately after closure of the tube, they divide rapidly, producing more and more neuroepithelial cells. Collectively they constitute the neuroepithelial layer or neuroepithelium. 12

13. Once the neural tube closes, neuroepithelial cells begin to give rise to another cell. These are the primitive nerve cells, or neuroblasts. They form the mantle layer, a zone around the neuroepithelial layer. The mantle layer later forms the gray matter of the spinal cord. 13

14. The outermost layer of the spinal cord, the marginal layer, contains nerve fibers emerging from neuroblasts in the mantle layer. As a result of myelination of nerve fibers, this layer takes on a white appearance and therefore is called the white matter of the spinal cord 14

15. BASAL, ALAR, ROOF, AND FLOOR PLATES As a result of continuous addition of neuroblasts to the mantle layer, each side of the neural tube shows a ventral and a dorsal thickening. The ventral thickenings, the basal plates, which contain ventral motor horn cells, form the motor areas of the spinal cord; the dorsal thickenings, the alar plates, form the sensory areas. 15

16. Development of the Spinal Cord 16

17. A longitudinal groove, the sulcus limitans, marks the boundary between the two. 17

18. The dorsal and ventral midline portions of the neural tube, known as the roof and floor plates, respectively, do not contain neuroblasts; they serve primarily as pathways for nerve fibers crossing from one side to the other. 18

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20. Development of the Medulla 20

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23. Differentiation of Forebrain 23

24. HISTOLOGICAL DIFFERENTIATION Nerve Cells Neuroblasts, or primitive nerve cells, arise exclusively by division of the neuroepithelial cells. further development becomes the adult nerve cell or neuron. 24

25. Axons of neurons in the basal plate break through the marginal zone and become visible on the ventral aspect of the cord. Known collectively as the ventral motor root of the spinal nerve, they conduct motor impulses from the spinal cord to the muscles. 25

26. Axons of neurons in the dorsal sensory horn (alar plate) behave differently from those in the ventral horn. They penetrate into the marginal layer of the cord, where they ascend to either higher or lower levels to form association neurons. 26

27. Glial Cells The majority of primitive supporting cells, the gliablasts, are formed by neuroepithelial cells and migrate from the neuroepithelial layer to the mantle and marginal layers. In the mantle layer, they differentiate into astrocytes Another type of supporting cell derived from gliablasts is the oligodendroglial cell. This cell, which is found primarily in the marginal layer, forms myelin sheaths around the ascending and descending axons in the marginal layer. 27

28. In the second half of development, a third type of supporting cell, the microglial cell, appears in the CNS. Neural Crest Cells During elevation of the neural plate, a group of cells appears along each edge (the crest) of the neural folds Crest cells migrate laterally and give rise to sensory ganglia (dorsal root ganglia) of the spinal nerves and other cell types 28

29. Development of meninges The dura mater arises from paraxial mesoderm that surrounds the neural tube. The pia mater and arachnoid mater arise from neural crest cells. 29

30. Neural crest 30

31. The neuropores The unfused anterior end of neural tube, is the cranial neural pore/rostral neuropore, it fuses on or before 26 days of development. The posterior neuropore/caudal neuropore fuses before the end of 4 th week. 31

32. Neural Tube Related Birth Defects Anterior neural pore Posterior neural pore failure to close = anencephaly failure to close = spina bifida 32

33. 33 Neural tube defects can be prevented If folic acid is given during pregnancy

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35. Neural crest forms part of peripheral nervous system (PNS) Neural tube becomes central nervous system (CNS) Somites become spinal vertebrae. Somites 35

36. Developmental anomalies of neural tube Neural tube defects can be detected by the presence of alpha-fetoprotein(AFP) in the fetal circulation after the 4 th week of development. Hydrocephaly, is huge collection of CSF in the ventricles of the brain as a result of blockage of ventricular passages. Microcephaly is small head resulting from failure of brain to grow normally due to radiation, infection by cytomegalovirus and toxoplasmosis gondii parasites. 36

37. Holoprosencephaly Failure of prosencephalon to divide into two cerebral hemispheres. Often associated with facial deformities: Single orbit with two eyes or one eye or no eye. Proboscis-type nose located above eye. Cleft lip and palate. 37

38. Migration failure of NCC Leads to mega colon, Hirshsprung’s disease. A developmental disease where the migration of neural crest cells stops and there is aganglionic segment of colon where there is absence of autonomic ganglionic connections. 38

39. Alzheimer’s disease There is an overall shrinkage of brain tissue. The grooves or furrows in the brain, called sulci, are noticeably widened and there is shrinkage of the gyri. In addition, the ventricles, or chambers within the brain that contain cerebrospinal fluid, are noticeably enlarged. In the early stages of Alzheimer's disease, short-term memory begins to fade when the cells in the hippocampus, which is part of the limbic system, degenerate.. 39

40. The ability to perform routine tasks also declines. As Alzheimer's disease spreads through the cerebral cortex (the outer layer of the brain), judgment declines, emotional outbursts may occur and language is impaired. 40

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