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NEUROEMBRYOLOGY
Formation of the Neural Tube and Neural Crest

3rd Week formation of endoderm, mesoderm and ectoderm Notochord

b. Secondary Neurolation day 20 to 42 formation of

coccygeal segment Caudal Eminence

sacral and cord from

stimulates ectoderm to thicken secretes cell adhesion molecules

Induction proper development of structure is dependent on proper development of neighboring structures Neurolation

becomes the neural plate and neural groove (from neural plate) of which both will function as one due to adhesion molecules becomes nucleus pulposus in adults as its remnants Neural groove and neural fold formation

Disorders of Primary (Dysraphic Defects)

a. Anterior Neuropore Closure Defects 1. Meroanencephaly / Anencephaly 2. Incomplete development of brain and calvaria 3. Abnormal Facies 4. Mircocephaly Note: Role of folic acid supplements is for prevention

Neurolations a. Primary Neurolation formation of Neural Crest (becomes the PNS) *Neural Crest Derivatives: a. Schwann Cells b. Cranial Nerve Ganglion c. Dorsal Root Ganglion d. Autonomic Ganglion e. Chromaffin Cells of Adrenal Medulla f. Pia and Arachnoid of meninges g. Melanocytes

b. Posterior

formation of Neural Tube (CNS) *Neural Tube Derivatives: a. Rostral 2/3 (Anterior Neuropore) brain b. Caudal 1/3 (Posterior Neuropore) spinal cord but up to lumbar only * Note: The anterior neuropore closes first duu to shorter travel distance at day 24 while the posterior part closes at day 26

Neuropore Closure Defects (Myeloschisis) 1. Sipina Bifida Oculta defect in vertebral arch fusion -region of occurrence is seen with tufts of hairs 2. Spina Bifida Cystica a. Meningocoele no nerve tissue protrusion b. Meningomyelocele involves nerve tissue protrusion 3. Myelorachischisis

Disorder of Secondary (Myelodysplasia)

Neurolation

caudal eminence involvement neural tube malformation

accompanied by unusual skin pigmentation, unusual hair growth, superficial capillaries and prominent dimple

1. Tethered Cord Syndrome

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- conus medullaris and filum terminale are abnormally fixed (immobilized)

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Ventricular zone becomes ependymal calls as remnants Marginal zone an acellular zone due to it only contains processes - becomes the white mater Intermediate zone (mantle layer) Alar plate (posterolateral part) for sensory function becomes the dorsal gray horn Basal plate ( ventrolateral part) for motor function - becomes ventral gray horn and lateral horn

4th Week formation of three Primary Vesicles 1. Forebrain ( Prosencephalon) 2. Midbrain ( Mesencephalon) 3. Hindbrain (Rhombencephalon)

5th Week

formation of Secondary Vesicles that originated from the primary vesicles) Secondary Caviti Derivative Wall Vesicles es Cerebral Lateral Telencephal Hemisph Ventric on Forebrain ere le (Prosencepha Third lon) Diencephalo Thalami Ventric n le Cerebr Midbrain Mesencepha al (Mesencephal --lon Aqued on) uct Upper Pons part of Metencepha and 4th lon Cerebell ventric um Hindbrain le (Rhombencep Lower halon) part of Myelenceph Medulla 4th alon ventric le formation of Flexures 1. Cervical between hindbrain and spinal cord 2. Midbrain- between forbrain and midbrain -AKA cephalic flexure 3. Pontine demarcates metencephalon and myelencephalon 4. Telencephalic between telencephalon and diencephalon

*Sulcus limitans demarcates alar plate and basal plate *Basal plate and Alar plate later become NUCLEI

Spinal Cord Derivatives a. Neural Cavity Spinal Cord b. Ventricular Zone Ependymal Cells c. Alar Plate Dorsal Gray Horn d. Basal Plate Ventral and Lateral Gray Horn e. Marginal Zone White Mater Guide for Innervation

Fibronectin molecules

and

Laminin

matrix

Integrins for recognition

*Spinal nerves develop connections by having integrins in their processes where these search for laminins and fibronectins found in connective tissues. When they do, hence, they reach end target organs Development of Medulla (Myelencephalon) - conformations are dorso-ventral in proximal 1/3 and medio-lateral in late 2/3

formation of cranial nerves IX, X, XI and XII 1. Alar Plate Derivative (Sensory
Function)

TRANSVERSE DIFFERENTIATION NEURAL TUBE

OF

PRIMITIVE

Gracile Nuclei Cuneate Nuclei Descending Nucleus of V Solitarius Nuclei (IX and X)

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Vestibular / Cochlear Nuclei Inferior Olivary Nuclei Basal Plate Derivative (Motor Function) -efferent in nature hence, motor

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Development of Midbrain (Mesencephalon) conformation is reverted to dorsoventral form

2.

3.

Hypoglossal Nuclei Ambiguus Nuclei

tongue deglutition

formation of cranial nerves III and IV 1. Neural Cavity Derivative: Sylvian

(*Cerebral) Aqueduct 2. Alar Plate Derivative Function) (Sensory

Dorsal Motor Nucleus of X Neural Canal / Cavity Central Canal / IV Ventricle

Inferior Colliculus Superior Colliculus Substantia Nigra Red Nucleus

- auditory - visual

Development of Pons (from Metencephalon)

formation of cranial nerves V, VI, VII and

VIII

1.

Alar Plate Derivative (Sensory Function) - in lateral conformation Rhombic Lip (Cerebellum) Sensory Nucleus of Trigeminal face only (V)

Mesencephalic Nucleus of V 3. Basal Plate Derivative (Motor Function)

Oculomotor Nucleus (III) superior Trochlear Nucleus oblique eye muscle (IV)

Pontine Nuclei 2. Basal Plate Derivative (Motor Function) - in medio-lateral conformation Abduccens nuclei lateral rectus of eye muscles Facial nuclei

Development of Forebrain (Prosencephalon)

develops

at 2nd month of gestation simultaneous with formation of facial structures from mesoderm

follows

an development

INSIDE

OUT

pattern to

of CNS

Motor Nucleus of Trigeminal muscles of mastication(V) 3. Neural Canal / Cavity IV Ventricle

Inf=ections

may predispose abnormalities T.O.R.C.H in formation diencephalon of

Prosencephalization sequence of events

telencephalon and

Development of Cerebellum Metencephalon) from rhombic lip conformation is still jn lateral form

(from

medio-

formation of an additional zone: External Germinal (Granular Layer) Zone from Marginal Zone - neurons migrate inward to form:

*Inside out pattern is where the first cell to develop is found inside *TORCH Toxoplasmosis, Others, Rubella, CMV, HSV *Holoproncephaly failure of prosencephalon to undergo cleavage Development of Telencephalon

Granule Cells Stellate Cells Basket Cells

formation of Primitive Tube

formation of cortical plate between the marginal zone and intermediate zone formation of sub-plate beneath the cortical plate

Intermediate Zone becomes internal granular layer; neurons migrate outward to form Deep Cerebellar Nuclei and Purkinje cells.

Development of Thalami (Diencephalon)

largely derived from Alar Plate 3 -VRVM

1st Shifting Lec 01 development occurs in OUTSIDE FIRST

sequence

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pattern of synaptic contacts occurs throughout life a. Overproduction of neurons and apoptosis role of nerve growth factors and fibroblast growth factors in interrupting apoptosis b. Axonal Outgrowth growth can reach distant targets through tropic factors c. Synaptogenesis requires right cues from target cell (synaptic stabilization)

establishment of an orderly map of the

sensory world in the Thalamic Nuclei ( Retinotopic and Tonotopic mapping)

gives rise to: Epithalamus Thalamus

establishes orderly map of the sensory world (retinotopic mapping, tonotopic mapping)

Hypothalamus

*Outside first sequence is when the first cell to develop will be placed outside. Development of Cerebral Cortex

follows INSIDE OUT pattern formation of cortical plate at interface of

marginal zone and intermediate zone formation

Mechanism of Plasticity alteration in selective neuronal cell death, axon simplification and retention of transient axonal branches and synapses that would otherwise be lost *An infant is more resistant to brain damage due to hypoxia because brain can still reclaim neurons that are programmed to die by mechanism of plasticity.

Marginal Zone gives rise to 1st Layer of

Cerebral cortex

Cortical Plate 2nd to 6th layer Sub-plate and Intermediate Zone gives
rise to sub-cortical white matter Gross Abnormalities Development of Cortical

Lissencephaly failure of gyri to forming smooth surface of cerebral cortex Pachygyria large gyri Microgyria small gyri Schizencephaly abnormal patterns of sulci and gyri with unilateral or bilateral clefts in cerebral hemispheres *A gyrus is like an inverted villi for increasing surface area. Therefore, it too increases the availability of neuronal space for neuronal development. Less gyrus, less neurons, therefore mental defect.

Critical Period time period when these types of plastic changes cease to occur. It usually starts at age of 3 but varies from region to region. *Likewise, neuronal apoptosis starts at age 3 because the cessation of mechanism of plasticity. Synaptic Development - parallels cellular development and migration Myelination - starts at 6 months to life - peaks from birth to first year - Affects leukodystrophies, phenylketonuria as well as nutrition (malnutrition) *New borns are having reflexes because myelination is not yet complete

Cellular Events in Brain Development Parameters in brain organization

density of neurons (which are about 100 billion) pattern of axon and dendrite branching

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Ventricular System Abnormalities Obstructive Non-Obstructive Hydrocephalus Hydrocephalus Non-Communicating Communicating Due to blockage in Due to abnormalities of the ventricular system the subarachnoid space ie.: Congenital ie.: Obliteration of Aqueductal Stenosis arachnoid villi

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