1. The DEVELOPMENT of the NERVOUS SYSTEM
Joselito B. Diaz, MD, FPNA
COLLEGE OF REHABILITATION SCIENCES

2. Origin of the Nervous System
At day 16 after conception, the embryo consists of three germ layers
Ectoderm
Mesoderm
Endoderm

3. Neural Plate
3rd week of development, in the dorsum of the embryo, a pear-shaped ectodermal plate rostral to the primitive knot developed
The nervous system developed from the neural plate

4. Neural Plate
Notochord and paraxial mesoderm induce the overlying ectoderm to differentiate into the neural plate

5. Primary Neurulation
Rapid cell proliferation at the margins of the neural plate
Neural groove forms between the neural folds

6. Primary Neurulation
Neural folds grow towards each other to form the neural tube
On the 22nd day, fusion begins at the level of the future lower medulla
Closure proceeds in cranial and caudal directions

7. Primary Neurulation
Rostral neuropore closes at the 25th day of gestation
Caudal neuropore closes at the 27th day of gestation
Rostral 2/3 – brain
Caudal 1/3 – spinal cord up to the lumbar area

8. Neural Crest
Cells from the lateral margin of the deepening neural groove
Not incorporated in the neural tube but forms temporarily a strip of ectodermal cells between the neural tube and the overlying ectoderm
Migrates to the dorsolateral aspect of the neural tube

9. Neural Crest
The neural crest cells give rise to the following structures
Dorsal root ganglia
Sensory ganglia of cranial nerves (CN V, VII, IX, X)
Autonomic ganglia
Chromaffin cells of the adrenal medulla
Schwann cells
Melanocytes
Arachnoid and pia mater
Mesenchyme of the branchial arches

10. Secondary Neurulation
Caudal neural tube formation i.e. sacral and coccygeal segments
Begins at 28th to 32nd day of gestation
Caudal eminence enlarges and cavitates
Attach to neural tube and cavity becomes continuous

11. Neural Tube Defects Result in various errors of neural tube closure
Accompanied by alterations of axial skeleton as well as of overlying meningovascular and dermal covering
Congenital malformations associated with defective primary neurulation are called dysraphic defects
Most dysraphic defects occur at the level of the anterior or posterior neuropore

12. Neural Tube Defects Dysaphic defects in order of decreasing severity
Craniorachischisis totalis
Anencephaly
Rachischisis
Encephalocele
Spina bifida
Congenital abnormalities associated with defective secondary neurulation are known as myelodysplasia

13. Craniorachischisis Totalis

14. Anencephaly

15. Rachischisis

16. Encephalocele

17. Encephalocele

18. Spina Bifida

19. Spina Bifida
Spina bifida occulta
Meningocele
Myelomeningocele

21. Tethered Cord

23. 3 Primary Brain Vesicles
Following closure of the anterior neuropore, rapid growth of neural tissue in the cranial region
On the 4th week of development, the cephalic end shows 3 dilatations, the primary brain vesicles, and 2 flexures

24. Primary Brain Vesicles
Prosencephalon (forebrain)
Mesencephalon (midbrain)
Rhombencephalon (hindbrain)
The caudal portion of the neural tube forms the spinal cord
The 3 part brain begins to assume a “C”-shape by the formation of the cephalic flexure at the level of the mesencephalon and the cervical flexure between the hindbrain and spinal cord
Primary Brain Vesicles

25. 5 Secondary Brain Vesicles
On the 5th week of development, the 3 part brain begins to develop 5 vesicles
The prosencephalon subdivides into two parts: telencephalon and diencephalon
At the cephalic flexure, the mesencephalon remains tubular and undivided
The rhombencephalon subdivides into two parts: metencephalon and myelencephalon

26. Secondary Brain Vesicles
The mesencephalon is separated from the rhombencephalon by a deep furrow, the rhombencephalic isthmus
The pontine flexure separates the metencephalon and myelencephalon

27. Primary Division of the Developing Brain
Primary vesicle
Primary division
Subdivision
Adult structures
Forebrain vesicle
Prosencephalon
Telencephalon
(lateral ventricles)
Cerebral cortex, subcortical white matter, amygdala, basal ganglia, hippocampus, olfactory bulb and tract
Diencephalon
(third ventricle)
Thalamus, hypothalamus, epithalamus, subthalamus, optic nerve and retina
Midbrain vesicle
Mesencephalon (cerebral aqueduct)
Mesencephalon
Midbrain
Hindbrain vesicle
Rhombencephalon
(fourth ventricle)
Metencephalon
Pons, cerebellum
Myelencephalon
Medulla oblongata

28. Development of the Spinal Cord

29. Neuroepithelium
After closure, cells of the original single layered tube divide to form a pseudostratified neuroepithelium
Also known as matrix cells

30. Neuronal Proliferation
Stem cells in the periphery replicate their DNA then migrate towards the cavity of the tube and divide; the two daughter cells then migrate back to the periphery
“to and fro migration”
Rate can be 250,000/min

31. First Wave of Proliferation
In the earliest phase, stem cells divide symmetrically to produce two additional stem cells
Later phase, asymmetrical division – 1 stem cell and 1 post-mitotic neuronal cell (neuroblast)

32. Intermediate or
mantle zone
Ventricular or
germinal zone

33. Second Wave of Proliferation
“Switch point”
Stem cells stopped making neuroblasts and produces glioblasts
The ventricular layer differentiates into the ependymal lining of the ventricles and central canal

34. Neuroblasts and Glioblasts

35. Neuroblasts give rise to nerve fibers that grows peripherally and form a layer external to the mantle zone called the marginal zone
Mantle zone will form the gray matter while the marginal zone will form the white matter of the spinal cord

36. Spinal Cord Development
As the spinal cord develops, neuroblasts in the mantle layer proliferate in 2 zones
In cross section the mantle layer develops a characteristic “butterfly”-shape of gray matter
The lateral walls of the tube thicken but leave a shallow, longitudinal groove called the sulcus limitans which separates the developing gray matter
Dorsal alar plate
Ventral basal plate

37. Spinal Cord Development
The neuroblasts in the basal plate will give rise to the motor neurons of the of the anterior horn
The neuroblasts in the alar plate will become the sensory neurons of the posterior horn
The lumen of the spinal cord becomes the central canal
Anterior median fissure and posterior median septum

38. Anterior (Ventral) Motor Roots of the Spinal Nerves
The medial group of motor neurons form large multipolar cells whose axons supply the musculature of the body
The lateral group of motor neurons give rise to autonomic preganglionic fibers (intermediolateral cell column)
T1-L2: sympathetic outflow
S2-S4: parasympathetic outflow

40. Posterior (Dorsal) Sensory Roots of the Spinal Nerves
The first neurons of the sensory pathway are derived from the neural crest cells
Each neuroblast (Dorsal root ganglion cell) develops 2 processes
The central processes enter the spinal cord
The peripheral processes join the motor axons and becomes the spinal nerve

42. The Sectional Organization of the Spinal Cord

43. Positional Changes of the Cord
In the first 2 months of development, the spinal cord extends the entire length of the vertebral column and the spinal nerves pass through the intervertebral foramina at their level of origin

44. Positional Changes of the Cord
With increasing age, the vertebral column lengthen more rapidly than the spinal cord
At birth, the terminal end of the spinal cord lies at the level of the 3rd lumbar vertebra
The anterior and posterior roots of the spinal nerves below L1 descend within the vertebral canal until they reach their appropriate exits through the intervertebral foramina

45. Positional Changes of the Cord
Filum terminale: the slender fibrous strand of pia mater which attach the coccygeal cord to the coccyx
Cauda equina: collectively, the anterior and posterior roots of the spinal nerves below L1 and the filum terminale

46. Development of the Brain

47. Development of the Brain
Neuroblasts of the brainstem develop in a manner similar to the spinal cord
From the medulla through the midbrain, alar and basal plates form motor and sensory columns of cells that supply cranial nerves
However, the organization of alar and basal plates differ from of the spinal cord in that
1) in the medulla and pons, the alar plate lies lateral to the basal plate, not dorsal to it, since the 4th ventricle is “open”
2) there are migrations of neuroblasts of both plates from the ventricular floor to other locations
The diencephalon and cerebral hemispheres develop from the alar plate
The cerebellum also develops from the alar plate

48. Medulla
The expansion of fourth ventricle moved the alar plates laterally
The neuroblasts at the basal plates form the motor nuclei of the CN IX, X, XI and XII
The neuroblasts of the alar plates form the sensory nuclei of the CN V, VIII, IX and X, the gracile and cuneate nuclei and the olivary nuclei

49. Medulla (Myelencephalon)
The roof plate of the myelencephalon consists of a single layer of ependymal cells covered by a vascular mesenchyme, the pia mater
The two combined are known as the tela choroidea
Vascular tufts of tela choroidea project into the cavity of the fourth ventricle to form the choroid plexus, which produces the cerebrospinal fluid

50. Medulla (Myelencephalon)
Local resorptions of the roof plate occur at the 4th and 5th month of development
Lateral foramina of Luschka and median foramen of Magendie
Escape of cerebrospinal fluid from the ventricles into the subarachnoid space

51. Pons (Metencephalon)
The pons arises from the anterior part of the metencephalon but also receives cellular contributions form the alar plate of the myelencephalon
The neuroblasts of the basal plate form the motor nuclei of the CN V, VI and VII
The neuroblasts of the alar plate form the sensory nuclei of the CN V, VII, VIII and the pontine nuclei
The axons of the pontine nuclei grow transversely to enter the developing cerebellum

52. Cerebellum (metencephalon)
Formed from the posterior part of the alar plates of the metencephalon
On the 5th-6th week of development, the rhombic lips project caudally over the roof plate of the fourth ventricle and unite with each other in the midline to form the cerebellar plate
By the 12th week, the plate shows the small midline vermis and two lateral hemispheres

53. Cerebellum
The neuroblasts from the ventricular zone migrates toward the surface of the cerebellum to form the cerebellar cortex
Other neuroblasts remain close to the ventricular zone and differentiate into the cerebellar nuclei (dentate, emboliform, globose and fastigial nuclei)

54. Midbrain (mesencephalon)
The midbrain is the least modified of the brainstem structures with regard to basal and alar plates
Neuroblasts of alar plates migrate to form the inferior and superior colliculi and the mesencephalic nucleus of CN V
Neuroblasts in the basal plates will form the motor nuclei of CN III and IV
The embryologic origin of the red nucleus and substantia nigra (from alar or basal plates) are uncertain
The cavity of the original neural tube is little modified in the adult midbrain except to be narrowed by growth of the surrounding midbrain structures; it remains as the narrow cerebral aqueduct
Midbrain (mesencephalon)

55. Diencephalon
The diencephalon develops from the median portion of the prosencephalon and consists of a roof plate and two alar plates but lacks the floor and basal plates
The most caudal part of the roof plate develops into the pineal body or epiphysis
The tela choroidea gives rise to the choroid plexus of the third ventricle

56. Diencephalon
The alar plates form the lateral walls of the diencephalon
The hypothalamic sulcus divides the plate into a dorsal thalamus and a ventral hypothalamus
With continued growth of the thalami, the third ventricle becomes narrowed and the two thalami may fuse forming the interthalamic connection or massa intermedia

57. Telencephalon
The telencephalon consists of two lateral outpocketings, the cerebral hemispheres and a median portion, the lamina terminalis
The lateral ventricles communicate with the third ventricle through the interventricular foramina of Monro

58. Cerebral Hemisphere
Each cerebral hemispheres arise at the beginning of the 5th week of development
At the basal part of the hemispheres, the corpus striatum arises
Dorsomedial portion, the caudate nucleus
Ventrolateral portion, the lentiform or lenticular nucleus (putamen and globus pallidus)

59. Cerebral hemispheres
The mesenchyme between the cerebral hemispheres condenses to form the falx cerebri
The cerebral hemispheres continue to grow and expand, first anteriorly to form the frontal lobes, then laterally and superiorly to form the parietal lobes and finally posteriorly and inferiorly to produce the occipital and temporal lobes
The cortex covering the lentiform nucleus, the insula, lags in growth and later overgrown by the adjacent temporal, frontal and parietal lobes

60. Cerebral Hemispheres
Ascending and descending tracts of the cerebral hemispheres pass between the thalamus and caudate nucleus medially and lentiform nucleus laterally
Collectively known as the internal capsule

61. Cerebral Cortex
The neuroblasts from the ventricular zone migrates toward the surface of the cerebral hemispheres to form the cerebral cortex
At the final part of fetal life, the surface of the cerebral hemispheres grows so rapidly that many gyri separated by fissures or sulci appear on its surface

62. Schizencephaly

63. Lissencephaly

64. Polymicrogyria

65. Commissures
The lamina terminalis forms a bridge between the two hemispheres and enables nerve fibers to pass from one cerebral hemisphere to the other
Anterior commissure: connects the olfactory bulb and the two temporal lobes
Fornix: connects the hippocampus in each hemispheres
Corpus callosum: massive connection between hemispheres
Optic chiasm: contains fibers from the medial halves of the retinae

66. Myelination in the Central Nervous System
Formed by the oligodendroglia
At 4th month of development, myelination begins in the sensory fibers in the cervical spinal cord and then extends caudally
Myelination in the brain begins at the 6th month but is restricted to the basal ganglia
At birth, the brain is largely unmyelinated
Myelination is not haphazard but systematic, occurring in different nerve fibers at specific times
Myelination within the CNS progresses most rapidly after birth and continues up to adult life

67. The DEVELOPMENT of the NERVOUS SYSTEM
Joselito B. Diaz, MD, FPNA
COLLEGE OF REHABILITATION SCIENCES