NEUROEMBRYOLOGY

1. NEUROEMBRYOLOGY Dr. Raymond Colello

2. Development of the Nervous System FACTS Develops between week 4 and adultdhood Nervous system develops from neural plate, which is derived from the ectoderm. From a few dozen cells, the brain becomes an organ weighing 800g at birth, 1,200g at 6 years of age, and about 1400 g in the adult. 3% of births are associated with major malformations of the CNS, 75% of spontaneously aborted fetuses and 40% of infants who die within the 1st year of life have major CNS malformations.

3. Gastrulation precedes Neurulation Mesodermal cells migrating cranially and coming to rest on the midline form the notochordal process This axial mesoderm induces the overlying ectoderm to form the neural plate The neural plate forms the brain and spinal cord by the process of folding called Neurulation

4. The entire CNS develops from the embryonic neural tube. Neural ectoderm on the dorsal aspect of the developing embryo gives rise to neural groove, neural folds, then fuses to form the neural tube. The neural crest pinches off dorsolateral to the neural tube, and gives rise to neural structures in the PNS. Day 22

5. Closure of the neural tube proceeds bidirectionally

6. Derivatives of Neural Tube vs. Neural Crest

7. Neural tube related birth defects Anterior neural pore failure to close = anencephaly Posterior neural pore failure to close = spina bifida 1:1000 births

8. Spina Bifida Spina bifida: developmental anomaly characterized by defective closure of the bony encasement of the spinal cord, through which the cord and meninges may or may not protrude. Rachischisis: abnormalities where neural folds fail to fuse

9. Anencephaly Congenital absence of cranial vault, with cerebral hemispheres completely missing or reduced to small masses. Anencephaly occurs in about 4 out of 10,000 births. The exact number is unknown, because many of these pregnancies spontaneously abort.

10. Early Development of the Brain (Day 26) The rostral end of the neural tube undergoes cephalization (developing brain) giving rise to three primary brain vesicles (prosen-, mesen- and rhomben- cephalon). Between the 4th and 8th weeks, the brain tube folds sharply at 3 locations: 1: Mesencephalic flexure 2: Pontine flexure 3: Cervical flexure

11. Further subdivisions of the brain vesicles creates 5 secondary vesicles

12. Brain vesicles, indicating the adult derivatives of their walls and cavities.

13. Histogenesis of cell of the CNS

14. Differentiation of Neural Tube Into Spinal Cord The mantle layer of the developing neural tube (primordial gray matter) gives into alar and basal plates, separated by the sulcus limitans. The alar plate differentiates into sensory nuclei of the CNS (dorsal horn of the spinal cord gray); the basal plate into motor nuclei (ventral horn of spinal gray).

15. Development of Spinal Cord and Derivatives of Neural Crest

16. Positional Changes of Spinal Cord Diagrams showing the position of the caudal end of the spinal cord in relation To the vertebral column and meninges at various stages of development. The Increasing inclination of the root of the first sacral nerve is illustrated.

17. Differentiation of the Neural Tube in the Medulla At the level of the developing medulla, the alar plate of the neural tube (gives rise to sensory nuclei) is displaced laterally, separated from the basal plate (motor nuclei) by the sulcus limitans. The roof plate thins out to become the posterior medullary velum and choroid plexus of the fourth ventricle. sulcus limitans A A B B

18. Further differentiation of the alar and basal plates occurs, dividing them into cell columns that ultimately break up into sensory and motor nuclei. Sulcus limitans GSA SSA GVA SVA alar GVE SVE GSE basal

19. Sensory & motor cell columns divide into sensory and motor nuclei with specific functional components. SL Sulcus limitans X XII ADULT MEDULLA

20. Differentiation of Neural Tube in the Pons and Cerebellum The dorsal part of the alar plate of each side forms the rhombic lip which becomes thickened to form the primordium of the cerebellum.

21. Differentiation of the Neural Tube in the Midbrain Red nucleus In the midbrain, the alar plate gives rise to the superior and inferiorcolliculi; the basal plate gives rise to the oculomotor and trochlear nuclei (GSE) and the Edinger-Westphal nucleus (GVE). The origin of the red nucleus and substantia nigra is controversial.

22. Differentiation of the Telencephalon As development proceeds, the cerebral hemispheres swell and grow posteriorly and Laterally to envelop the diencephalon. The olfactory bulbs sprout off the ventral Surfaces of each telencephalic vesicle.

23. Structures in the telencephalon (cerebrum, striatum) and diencephalon (thalamus, hypothalamus) are thought to arise from the alar plate. Derivatives of the basal plate are uncertain.

24. DEVELOPMENTAL ANOMALIES

25. Encephalocoele hernia of the brain; protrusion of the brain substance through a congenital opening in the skull

26. Meningocoele: cyst with meninges only Meningomyelocoele: meninges and spinal cord

27. Meningomyelocele

28. Developmental polymicrogyria Lissencephalia (agyria)

29. Porencephaly cysts or cavities in the brain, communicating by a “pore” with the subarachnoid space

30. Developing corpus callosum Lamina terminalis After the appearance of the cerebral hemisphere, the lamina terminalis becomes thickened to form the commissural plate through which fibers course to form the commissures: corpus callosum, anterior commissure, hippocampal commissure.

31. Agenesis, corpus callosum

32. Agenesis, corpus callosum

33. Communicating Hydrocephalus- impaired CSF reabsorption in the arachnoid granulations; obstruction of flow in the subarachnoid space Non-communicating hydrocephalus- caused by obstruction of flow within the ventricular system