L46. Development of CNS

• Early development of the nervous system involves several key steps
• The notochord induces the ectoderm to thicken, forming the neuro-ectoderm
• This transforms into the neural plate which folds to create the neural groove
• The neural groove fuses, forming the neural tube through primary neuralation
• The caudal eminence connects with the neural tube, developing the sacral and coccygeal spine via secondary neuralation
• Closure of cranial and caudal neuropores is crucial
• Roof and floor plates guide axon crossing

Early Division and Migration

• Cells of the neural tube differentiate into ventricular and marginal zones
• Mature neurons migrate along radial glia, forming the intermediate (mantle) zone

Neural Crest Cells

• These cells originate from the edge of the neural plate migrating to form various structures
• Structures include dorsal root ganglia (DRG), adrenal medulla (catecholamine cells), Schwann cells, and pia/arachnoid mater

Hirschprung's Disease

• This condition results from defective migration of neural crest cells
• It leads to a failure of parasympathetic (PANS) ganglia formation in the colon/rectum, causing non-innervated areas to contract and dilation above (megacolon)

Pharyngeal (Brachial) Arches

• Mesodermal outpouchings develop muscles, bones, and nerves in the head and neck
• Arch I (mandibular) associates with cranial nerve V (trigeminal)
• Arch II (hyoid) associates with cranial nerve VII (facial)
• Arch III associates with cranial nerve IX (glossopharyngeal)
• Arches IV & VI associate with cranial nerve X (vagus)

Brain Vesicles and Spinal Cord Development

• The prosencephalon (forebrain) differentiates into the telencephalon (cerebral cortex, basal ganglia) and diencephalon (thalamus & hypothalamus)
• The mesencephalon remains the midbrain
• The rhombencephalon (hindbrain) divides into the metencephalon (pons & cerebellum) and myelencephalon (medulla with 8 rhombomeres)

Brain Flexures

• Involve the cervical (myelencephalon-spinal cord), cephalic, and pontine (metencephalon-myelencephalon) regions

Abnormal CNS Development

• Can arise from genetic mutations or external factors like infection, nutrition deficiencies (iodine, folic acid), or fetal alcohol syndrome

Caudal Neuropore Closure Defects

• Spina bifida occulta is a hidden defect
• Meningocele involves meninges protruding
• Meningomyelocele involves meninges and neural tissue protruding
• Rachischisis is the lack of neural tube development, the most severe form

Cranial Neuropore Closure Defects

• Meningocele presents with meninges outside the skull
• Meningoencephalocele involves protrusion of meninges and brain tissue
• Meningohydroencephalocele involves protrusion of meninges, brain tissue, and part of the ventricle
• Anencephaly results in the forebrain not forming

Late Development of the Nervous System

Molecular Regulation of Differentiation

• Multipotent stem cells differentiate into neurons, astrocytes, and oligodendrocytes
• Dorsal signaling involves bone morphogenetic protein (BMP) and transforming growth factor beta (TGFβ)
• Ventral signaling involves Sonic hedgehog (SHH)
• Spinal cord and hindbrain regulation involves HOX genes
• Midbrain and forebrain regulation involves LIM1 and OTX2

Axonal Pathfinding

• Growth cones sample the environment with filopodia
• Direction is determined by interaction with molecules in the extracellular matrix (ECM) and other cells, such as NOGO and NCAM

Synapse Formation

• Synapses are overproduced initially, then pruned
• They are then modified throughout life

Myelination

• Activity and axon size dependent; motor/sensory tracts myelinate first and continues through one's 30's

Apoptotic Cell Death

• Massive normal cell death (~50%) occurs as cells compete for growth factors and target sites

Behavior Development

• Behavior supports activity-dependent development

Critical Period

• A time in development when normal input is required to achieve optimal function of a skill or ability

Spinal Cord Development

Organization

• Consists of repeating segments related to dermomyotomes (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygea)

Cell Columns

• Form in the intermediate zone, divided into alar and basal plates by the sulcus limitans
• The marginal zone becomes the white matter of the spinal cord
• The neural canal gives rise to the central canal and ependymal cells

Alar Plate

• Contains general somatic afferent (GSA) and general visceral afferent (GVA) cell groups

Basal Plate

• Contains general visceral efferent (GVE) and general somatic efferent (GSE) cell groups

Cell Group Arrangement

• From anterior (ventral) to posterior (dorsal): GSE, GVE, GVA, GSA

Axon Outgrowth

• The basal plate develops slightly earlier than the alar plate
• Motor axons initially grow to myotubes forming muscles
• Sensory axons from the neural crest follow motor axons

Differential Growth of Spinal Cord and Vertebral Column

• The spinal cord stops growing before the vertebral column
• The cauda equina of spinal nerves below arises
• The filum terminale = continuation of pia in the lumbar cistern

Functional Groups of Cranial Nerve Nuclei

• Expansion of the roof plate leads to the addition of special visceral efferent (SVE), special visceral afferent (SVA), and special somatic afferent (SSA) groups
• SVE and GSA migrate away from the ventricle

Development of the Myelencephalon (Medulla)

• The roof plate expands and the alar plate becomes lateral to the basal plate
• This addition creates SVE, SVA, and SSA groups
• Nuclei groups include the caudal spinal nucleus of cranial nerve V, the mid dorsal motor nucleus of X, the nucleus solitarius (IX, X), rostral inferior salivary nucleus (IX), the nucleus ambiguus (IX, X), the solitarius (VII, IX, X), spinal nucleus of cranial nerve V, and cochlear and vestibular nuclei (VIII)

Development of the Metencephalon (Pons & Cerebellum)

• The roof plate expands and the alar plate becomes lateral to the basal plate, adding SVE, SVA, and SSA groups
• Pons: caudal = abducens nucleus (VI), superior salivary nucleus (VII), facial nucleus (VII), spinal nucleus of V, vestibular Nuclei (VIII); mid = motor nucleus V, mesencephalic nucleus V, chief nucleus of V; rostral = mesencephalic nuclei of V
• Cerebellum: edge of the alar plate thickens to form the rhombic lip expanding to form the cerebellum (ant., post., & flocculonodular nodes)

Chiari Malformations

• A congenital condition affecting the brain
• Type 1 involves herniation of cerebellar tonsils, potentially leading to syringomyelia
• Type 2 involves herniation of cerebellar tonsils and the brainstem
• Type 3 is the most severe, potentially with occipital meningoencephalocele and hydrocephalus

Dandy Walker Syndrome

• Characterized by partial/complete absence of the cerebellar vermis and an enlarged 4th ventricle
• Associated with lack of motor coordination and potential hydrocephalus

Development of the Mesencephalon (Midbrain)

• The alar plate forms the tectum above the cerebral aqueduct; the superior colliculus relates to vision (rostral midbrain), and the inferior colliculus relates to hearing (caudal midbrain)
• The basal plate consists of the trochlear (IV) and oculomotor (III) nuclei, plus the Edinger-Westphal nucleus (III)

Development of the Diencephalon (Thalamus & Hypothalamus)

• The cerebral aqueduct opens to form the long, narrow 3rd ventricle
• The alar plate thickens into the thalamus and hypothalamus separated by the hypothalamic sulcus

The Development of the Telencephalon (Cerebral Cortex & Basal Ganglia)

• The basal ganglia are masses of cells lining the forebrain which is then divided by the internal capsule to separate the caudate from the lentiform nucleus
• Growth of the cerebral cortex: the anterior portion results in the frontal lobe, the posterior portion creates the occipital lobe and the posterior horn of lateral ventricle, and C-shaped growth produces the temporal lobe, hippocampus, and choroid plexus
• Formation of gyri & sulci increases cortical surface area

Lissencephaly

• A rare brain malformation, "smooth brain", thin cortex with few gyri
• Commonly induces mental retardation and associations alongside various genetic defects