In

the process of the formation of neural tube, not all of the neuroectodermal cells are incorporated. Clusters of cells that are not incorporated are called neural crest cells. o Derived from junction of skin ectoderm and neuroectoderm o Separate from neural tube o Adult equivalent: ganglia clusters of neurons found outside nervous system (e.g. dorsal root ganglia, superior mesenteric ganglion, coeliac ganglion) o Note: there are also ganglia inside the cranium (with the brain); largest = trigeminal ganglion

EVAGINATIONS AND PROTRUBERANCES

Figure 7. Evagination of the diencephalon and telencephalon. A. Diencephalon: 1 - Pineal Gland; 2 Posterior Pituitary gland or Neurohypophysis; 3 Anterior Pituitary gland or Adenohypo- physis; 4 - Optic bulb B. Telencephalon: 5 - Olfactory bulb; 6 - Cerebral hemispheres; 7- Temporal lobe Formation of neural groove is by invagination. Biggest evagination: Telencephalon The development of cerebrum, eyes, and ears is due to evagination from prosencephalon after the flexure.

SEGM ENTATION
Segmentation happens because some of the parts of the brain grow faster than others (i.e. the rostral forms faster than caudal hence it is more bulbous) Figure 5. Three primary transverse segments and five secondary segments of the brain

NEURONAL PROLIFERATION NEURONAL PROLIFERATION

Peak Time Period: 3-4 months AOG (age of gestation) Major Events: o Ventricular zone and the subventricular zone of the embryo are the sites of proliferation. o Proliferative units are produced by symmetrical divisions of stem cells and enlarge by asymmetrical divisions before migration. Neurons that are located in specific areas will start to grow. Telencephalon neurons grow faster than the olfactory and optic neurons; otherwise, the olfactory and optic neurons will be bigger. Other cellular elements inside the brain: glial cells, blood vessels Brain has many neurons but more supporting cells. Primitive ectodermal cells proliferate in the ventricular zone. Many neurons are at the cerebral cortex which came from the ventricular and subventricular zone (site of proliferation) When they start to proliferate, they become too crowded. They often go outward, migrating to specific destinations outside the brain. Genetic template is responsible for sending directions regarding the specific destinations of the neurons.

Three primary segments rd (3 week) Prosencephalon (forebrain) Mesencephalon (midbrain) Rhombencephalon (hindbrain)

Five secondary segments th (7 week) Telencephalon Diencephalon Mesencephalon Metencephalon Myelencephalon

Modern names/ prominent structures Cerebral hemisphere Thalamus & Hypothalamus Midbrain Pons & Cerebellum Medulla

FLEXURES
Figure 6. Flexures of the 3-segment and 5-segment brain

CYTOGENESIS AND HIST OGENESIS IN THE W ALL OF THE NEURAL TU BE

Pluripotent primitive blast cells (primitive neuroectodermal blast cells) proliferate in the periventricular neuroepithelium. Primitive blast cells produce neuroblasts and glioblasts, the most primitive groups of cells in the brain. Figure 8. Neuron formation

The brain is thrown into folds because it is inside the cranium. A flexure is a bend along the neural tube. It is needed to maximize the space for the brain. First to appear: cervical flexure - demarcates rhombencephalon and spinal cord. This disappears later on. Second to appear: cephalic flexure - demarcates prosencephalon and mesencephalon. Caudal part: fuse as a tubular structure spinal cord Rostral: evagination development of cerebral hemisphere

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DIFFERENTIATION

V VI

Inner pyramidal Polymorph

Large pyramidal cells (Betz cells) Fusiform cells

Primary motor cortex: Most important layer is the layer of neurons where corticospinal tract fibers would originate, since they are responsible for motor movements: layer 3 and 5. Layer 5 is more important because this is where Betz cells are located. Primary sensory cortex: Most important layer: layer 4 Functionally: o Corticospinal tract - efferent (layer 3 and 5) o Layer 2 and 4: receiving neurons, they are sensory, receiving impulses thalamus spinal cord peripheral environment

lines the ventricular wall

part of the blood brain barrier

like scavengers, security guard, garbage collector, MMDA of our brain (Chua, 2011)

Two Ways of Classification 1. Cytoarchitectonic organization based on cell types 2. Myleoarchitectonic organization based on myelin staining Figure 11. Layers of the cortex and associated cells

N EURONAL MIGRATION
Peak time: 3-5 months AOG Major events: o Development of cerebrum radial migration: cerebral cortex, deep nuclei (nuclei of basal ganglia) o Development of cerebellum radial migration: Purkinje cells, dentate nuclei tangential migration: external---internal granule cells; realignment along cerebral cortex In the process of migration, in the cerebral cortex, you end up with 6 layers of neurons. (subcortex = fibers of neurons) In the cerebellum = 3 layers of neurons

Parietal cortex: mainly sensory Frontal cortex: mainly motor Primary motor: efferent Primary sensory: afferent Calcarine cortex: layer 4 (external band of Ballarger) that is going to be very prominent because it subserves a special sense, vision; most visible band (seen by naked eye line of Gennari)

HIPPOCAM PUS
Seahorse shape (cross-sectional view); banana or tamarind shape (grossly) Found embedded on the floor of the temporal horn of lateral ventricle Composed of three-layered cortex: o Multiform o Pyramidal o Molecular
Another layer corresponds to dentate gyrus

Migration of the Neuroblasts Very important for proper cerebral cortex formation Neuroblast may: 1. Remain or move a short distance - these are neurons found in basal ganglia and cerebellum as well as part of the reticular formation in the brain stem; or 2. Migrate outward into the surface - to form the cerebral and cerebellar cortex

CORTICAL LAYERS
CEREBRUM
Table 1. Layers of the cortex
Layer Number I II III IV Cytoarchitectonic Name Molecular External granular External pyramidal Inner granular Principal Cell Type Axons and dendrites Small pyramidal cells Medium pyramidal Stellate cells

Neurons of hippocampus, especially of the CA1 segments, are the first to disappear when there is lack of oxygen (anoxia). Main function: memory; losing these neurons: loss of memory

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 Figure 12. Hippocampus. CA = Cornu almonis aka summer sector

CEREBELLUM
Recall: Three peduncles of the cerebellum o Superior or Brachium conjunctivum o Middle or Brachium pontis o Inferior or Restiform body Figure 13. Cerebellum Molecular o Large number of neuronal processes o There can be many dendritic processes, yet only one axonal process. o Only one axon (single process) dividing into axon terminals when it reaches its innervation organ

CONFIGURATION OF THE SPINAL GRAY M ATTER

Sulcus limitans divides the neural tube into dorsal and ventral regions. It is not apparent in the adult brain. Alar plate is dorsal to the sulcus limitans. o Neurons here are related to sensory function. o Afferent nerves - toward the CNS Basal plate is ventral to the sulcus limitans. o Neurons here are related to motor function. o Efferent nerves - away from the CNS

o Innervation of muscle fibers - axon divides into 6 axon terminals. Purkinje cell layer - layer of big Purkinje cell neurons that lines the cerebellar cortex in one straight line Granular cell layer

Figure 15. Spinal gray matter

ORGANIZATIONS
Peak time: 5 months AOG to postnatal Association fibers (U fibers) of cerebral cortex connects structures in the same hemisphere Major Events o Lamination - alignment, orientation and layering of cortical plate neurons o Neurite outgrowth - dendritic and axonal ramifications o Synaptogenesis - two neurons talk to each other synaptic connection o Cell death and selective elimination of neuronal processes and synapses o Glial proliferation and differentiation Astrocytes for structure and rapid transport of ions Oligodendrocytes for myelin formation Microglial cells acts as scavengers (usually through phagocytosis)

Figure 14. Cortical layers of the cerebellum

SPINAL CORD FORMATION

Three concentric layers (from the inside-out): o Ependymal layer - wall of recently closed tube (central canal) composed of ependymal cells o Mantle layer - forms nucleated gray matter of the spinal cord o Marginal layer - forms white matter of the spinal cord

MYELINATION
Last phase Peak time: birth to postnatal Major events: o Oligodendrogial proliferation o Glial cell - differentiate to be an oligodendrocyte, main function is to produce myelin CNS: Oligodendrocyte (wraps 3-4 axons); PNS: Schwann cell (wraps 1 axon). Which cell is more effective? In terms of the number of axons they myelinate, oligodendrocites appear to be more effective. However, the Schwann cells proliferate faster thus both cells may have the same efficiency.

Neurulation - occurs around day 20 or 21 (during the third week of development)

Why are the white and gray matter interchanged in the spinal cord and cerebral hemisphere?

As far as origin is concerned, they all originated from primitive epithelium that lies in the ventricular cavity and subventricular zone. In the development, neurons migrated outwards very fast and their processes are thrown from inwards

Process of migration in cerebral cortex is the reason why gray matter is more lateral than the white matter.

In the spinal cord, however, there is negligible migration that is why gray matter is inside and white matter is outside.

Anatomy of spinal cord: White matter (outside) Anatomy of cerebral hemisphere: Gray matter(outside)

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6. Craniomyeloschisis exposed brain and spinal cord

Disorders of Ventral Induction 1. Facial - telencephalic malformations (cleft lip or cleft palate) 2. Holoprosencephaly

Figure 16. Axon hugging by Schwann cell. What did the Schwann cell say to the axon? Oooooooohhh youre still bare. Let me embrace you. (Chua, 2011)

SUMMARY

Disorders of Neuronal Proliferation 1. Microcephaly vera - well-formed but very small brain 2. Macrocephaly vera - well-formed but unusually large Associated with: neurocutaneous syndromes (tuberous sclerosis, neurofibromatosis, Sturge-weber) : Achondroplasia : Beckwith syndrome

Table 2. Stages of embryonal development of the brain

Dorsal induction Ventral induction Neuronal proliferation Migration Organization Myelination

3 - 4 weeks AOG 5 - 6 weeks AOG 2 - 4 months AOG 3 - 5 months AOG 6 months AOG - years postnatal Birth - 2 years postnatal

Dorsal induction - must be complete to prevent the onset of abnormalities of the back. e.g., sinus, lump Ventral induction - responsible for facial development and organization Neuronal proliferation o (- -) - microcephaly o (++) - macrocephaly Organization - Development of axons, dendrites, and the connection between them (synapse) Myelination - for fast transmission of impulses and insulation for the axons

Abnormalities in the nervous system may also manifest on the skin as these two organ systems are derived on the same germ layer (ectoderm). Disorders of Neuronal Migration 1. Schizencephaly - cleft in surface of cortex 2. Lissencephaly - no convolutions smooth surface 3. Heterotopias - gray matter in white matter area (topias) 4. Pachygyria - big convolutions 5. Micropolygyria - small and more than the normal number of convolutions

Milestones Table 3. Detailed neuroembryonic development (no need to memorize )

Neural plate Neural groove and tube Optic vesicles Formation of neural crest Closure of the anterior neurophore Closure of the posterior neurophore Ventral horns appear Anterior and posterior roots Formation of primary flexures 3 primary vesicles Beginning of myelination 5 vesicle stage Formation of rhombic lips Formation of CNS Formation of pontine flexure Formation of commisures Migration completed Formation of major fissures Primary cerebral fissures appear Secondary cerebral fissures appear Formation of 6-layered cortex Myelination almost completed

Disorders of Neuronal Organization (abnormality seen in microarchitectural level) 1. Primary disturbance a. Mental retardation + seizures b. Trisomy 21 synapse dysfunction 2. Associated disturbances a. Congenital rubella - viral infection (Rubella virus) affecting fetal brain b. Phenylketonuria c. Trisomy 13 - 15 d. Rubenstein-Taybi syndrome

16 days 18 days 21 days 22 days 24 days 26 days 27 days 31 days 3-4 weeks 4 weeks 4 weeks 5 weeks 5-6 weeks 5-6 weeks 6 weeks 10 weeks 5 months 5 months 5 months 6 months 6-8 months 2 years
st

Disorders of Myelination 1. Cerebral white matter hypoplasia 2. Leukodystrophies a. Alexanders disease b. Canavans disease c. Krabbes disease d. Metachromatic leukodystrophy e. Sudanophilic leukodystrophy

*NOTE: Dismyelinating - disorder during myelin formation, no normal myelin formed Demyelinating normal myelin formed but structural damage to myelin happened

END OF TRANSCRIPTION Rae: Hello to 2016!!! We are a few steps away from the sem break! Yey! Special greetings to my constant seatmates Harold and Billy, to Team China, MDL 11, Pascos Angels and IILE mates! Oh and to end my greeting heres Dr. Chuas quotable quote for the day: We were all created from one of the happiest moments of our parents Fres: I miss Team China! Hello sa Christmas committee! Hannah: Hi guys! This is my first real greeting! Hi to my forevermates, Pascos Angels, anatomates, BioDil people and everyone else I havent had the chance to talk to yet. I was watching Pretty Little Liars yesterday and came across this nice quote, You must give up the life you planned in order to have the life that is waiting for you. Joseph Campbell. Hope this means something for some of you guys! Study hard and happy sembreak!

Development of CNS occurs early in pregnancy, during 1 trimester. Born with cleft palate - ventral induction problem Failure of organization - child with Down syndrome

CLINICAL CORRELATIONS: NEURO - DEVELOPMENTAL ANOMALIES

Failure of Dorsal Induction (Neural tube defects) 1. Craniorachischisis totalis - exposed brain 2. Anencephaly - no brain 3. Myeloschisis - exposed spinal cord 4. Encephalocoele - protrusion of brain through the skull 5. Myelomeningocoele, Arnold-Chiari malformation - membrane and parts of spinal cord are exposed

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