Human Nervous System Embryologic Development
- Neurons store and process info (can conduct action potential)
- Glial cells provide structural and metabolic support
- CNS -> Brain & Spinal Cord
- Brain -> Medulla, Pons, Cerebellum, Midbrain, Diencephalon, Cerebral Hemispheres
- CNS protected by skull and vertebral column and 3 meninges (dura mater, arachnoid, pia mater)
- CSF made in ventricles and fills them, emerges from apertures in 4th ventricle to subarachnoid space
- 4 Ventricles -> 2 lateral, 3 (diencephalon) & 4 (behind pons and medulla) connected by Cerebral Aqueduct -> central canal
- Ventricles 1 and 2 are connected to 3 via the Interventricular Foramina of Monro
Formation of Neural Tube
- Neurulation -> Formation of neural plate; begins week 3, ends by week 4
- Embryo referred to as neurula
- Neural Plate: Polarity, Bilateral Symmetry, Regionalization
- Notochord induces surface ectoderm to form Neural Plate
- Neural Groove -> Neural Folds -> Neural Tube
- Neural Crest Cells move ventrally and then laterally; will become epidermis and melanoblasts
- Tube Fusion begins around somites 4-6
- Anterior & Posterior neuropores connect central w/ amniotic cavity
- Ant neuropore closes @ day 25; Post neuropore closes @ day 27
- Rostral 2/3 neural tubeàbrain; Caudal 1/3àspinal cord
- Central lumenàcentral canal and ventricles
- Neural Crest Cellsà sensory ganglia of spinal & cranial nerves, schwann cells, pia & arachnoid mater
- Polarity, Bilateral Symmetry and Regionalization
Stages of Neural Tube Development
- 3 primary brain vesicles formed by fusion of neural folds & closure of rostral neuropore: Hindbrain, Midbrain, Forebrain
- 5th week forebrain & hindbrain divide into two giving 5 vesicles
Brain Flexures
- Cervical Flexure: junction of spinal cord and hindbrain
- Cranial/Cephalic Flexure: junction of midbrain and forebrain
- Pontine Flexure: thinning of roof of hindbrain (accordion look)
Histogenesis
- Neural tube columnar epithelium divided into ventricular, intermediate (mantle) and marginal zones
- Walls of the neural tube will first produce neuroblasts and then glioblasts
- Ventricular zone produces: ependymal cells, neurons, glial cells
Formation of Meninges
- Meninges around CNS from mesenchyme around neural tube
- Primitive Meninx: outer part forms dura mater; inner part form leptomeninges separated by Subarachnoid space (arachnoid and pia)
Myelination of Nerves
- PNS: Schwann cells derived from neural crest cells 1:1 ratio
- CNS: Oligodendrocytes many axons are wrapped by one
Spinal Cord
- Proliferation and differentiation of neuroepithelial cells results in thick walls and thin roof and floor plates
- Proliferation of lateral walls gives Sulcus limitans-divides dorsal from ventral on each side
- Alar Plate -> dorsal and afferent (sensory)
- Basal Plate -> ventral and efferent (motor)
- Vertebral column and dura mater grow more rapidly than spinal cord, therefore, its shorter and ends @ L1/L2
- Cauda Equina is the bundle of roots of the lumbar and sacral segments that extend lower than the spinal cord
- Lumbar Cistern is filled with CSF is the space around the cauda equina
- Filum terminale: fibrous thread of pia mater that extends from spinal cord to first coccygeal vertebra
The Myelencephalon (Medulla)
- Alar plate: sensory nuclei, inferior olivary nuclei, solitary nucleus, spinal trigeminal nucleus, cochlear and vestibular nuclei
- Basal plate: motor nuclei, hypoglossal nucleus, nucleus ambiguous, dorsal motor nucleus of vagal nerve, inferior salivatory nucleus of the glossopharyngeal nerve
- 4 afferent from alar plate and 3 efferent from basal plate
The Metencephalon (Pons and cerebellum)
- Alar plate: afferent nuclei, pontine nuclei, cerebellum
- Basal plate: efferent nuclei
Cerebellum
- Metencephalon->Cerebellum->Posterolateral fissure->Cranial & Caudal
- Cranial-> Medial swelling, the Vermis; lateral cerebellar hemispheres
- Caudal-> flocculonodular lobe (primitive part of the cerebellum)
- Primary fissure divides the cranial portion into an ant & middle lobe
The Mesencephalon (Midbrain)
- Alar plate: inferior and superior colliculi
- Basal plate: red nucleus, reticular nuclei, substantia nigra (origin unknown)
The Diencephalon
- Thalamic nuclei: sensory relay, derived from alar plate, located medially
- Hypothalamic nuclei: homeostatic funct & endocrine, alar & basal plates, give rise to mamillary bodies, located ventrally
- Epithalamic nuclei: pineal gland, habenuela, alar & roof plates, located dorsally
The Pituitary Gland
- 2 Sources: upgrowth of ectoderm from roof of stomodeum->anterior lobe (adenohypophysis)
- downgrowth from the neuroectoderm of the diencephalons->post lobe (neurohypophysis)
The Telencephalon (Cerebral Hemispheres)
- Floor of each hemisphere expands to form: striatum (caudate and putamen), amygdala & hippocampus
- Globus pallidus originates from roof plate of diencephalons
- One additional zone is added to the three previous ones, the subventricular zone
- Cells from subventricular zone will migrate into the marginal zone to give rise to cortical layers, as cerebral hemispheres expand, they cover the diencephalons, midbrain & hindbrain
- WHITE MATTER BETWEEN 2 NUCLEI (Caudate and Lentiform) ON ADULT BRAIN
Commissures
- Fiber bundles that connect two hemispheres: anterior commissure, hippocampal commissure & corpus callosum
C-Shaped Development, Gyri & Fissures
- Hemispheres grow caudal and then turn ventrally and rostrally to form temporal lobe, thereby having a C shape
- Month 4: no gyri or sulci are present (lissencephalic)
- Month 8: all major sulci present (gyrencephalic)
Choroid Plexus
- From the roof plates of the rhombencephalon & diencephalons; choroid fissure of telencephalon
General Nervous System Defects
- Nerve cells originate by means of an initial step in development called determination.
- Ectoderm -> Neuroectoderm accomplished by the end of gastrula stage
- Transforming factors: activin and fibroblast growth factors
- The development of regional specificity along the AP axis originates from interactions between the notochord and mesoderm, and ectoderm.
- After neuroectoderm is specified…not reversible
- Differentiation -> 1. proliferation and generation of specific classes of neurons, 2. migrate of cells to characteristic positions, and 3. maturation of cells and the development of specific interactions
- Intrinsic and extrinsic factors control differentiation
- Brain segmentation is apparent ONLY during early development…dependent of mesodermal tissue
- Spinal cord segmentation-SOMITES
- Hindbrain segmentation-RHOMBOMERES (8) -> each rhombomere is not associated with a single pair of sensory and motor cranial nerve roots…nerves exit on even-numbered rhombomere
- Forebrain Segmentation-Six or seven morphological NEUROMERES, but their significance remains unclear
- AP axis -> HOX Genes
- 4 clusters with 13 genes in each group
- 3′ cranial structures vs 5′ posterior structures
- Dorsal-Ventral Axis -> Sonic Hedgehog (with cholesterol as a cofactor)
- SHH is secreted by the notochord and influences the VENTRAL patterning
- BMP 4 and 7 are nonNEUROECTODERM and contribute to DORSAL patterning
- PAX genes are intermediate transcription factors to close neural tube
- Hindbrain à AP (HOX B except B1)…DV (SHH)
- Midbrain and Forebrain (HOX regulated)…L1M1 is expressed in the prechordal plate and OTX2 is expressed in the neural plate to designate the forebrain and midbrain…DV patterning by SHH occurs too…see above
- FGF-8 is the key signaling molecule inducing subsequent gene expressions that regulate differentiation in the anterior neural ridge and the isthmus (between the hindbrain and midbrain)
- Homeotic Transformation: change in the combinatorial code of a given somite
- Spina bifida occulta: closure of the caudal neuropore generally occurs in L5 or S1…single open vertebral arch defect with the presence of tuft of hair…no clinical symptoms
- Spina bifida cystic: determine by ultrasound and fetoprotein levels
- Spina bifida meningocele: when only meninges protrude…2 or more vertrebral arches may be affected
- Spina bifida meningomyelocele: when spinal cord and meninges protrude
- Spina bifida myeloschisis: when spinal cord is opened
- Anencephaly (meroanencephaly)…it means no brain but not true because there are some portions of the brain…failure of closure of the rostral neuropore
- Cranium Bifidum:
- Cranial meningocele: only the meninges
- Meningoencephalocele: meninges and part of brain
- Meningohydroencephalocele: meninges, brain, and ventricular system
- Arnold-Chiari…ventricular system is extended and interference with CSF…herniation of the vermis of the cerebellum
- Hydrocephalus is an imbalance between production and absorption of the CSF resulting in too much fluid in the ventricular system…not excess of CSF
- Hydraencephaly is an absence of cerebral hemisphere and occlusion of carotids
- Radial migration of cells is favored by the arrangement of basic columnar cells
- Layered structures (RADIAL ONLY), layered structures (radial and tangential…example the retina and spinal cord), and non-layered structures (brainstem and diencephalons)
- Radial glial cells are one of the first cells to express markers of differentiation
- Cytodifferentiation of the cortex (top to bottom):
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- Marginal zone
- Cotical Plate
- Subplate Layer
- Intermediate Zone
- Subventricular zone
- Ventricular Zone
-
- Order of Layer Formation
- VZ -> MZ -> IZ -> CP -> SVZ -> SPL
- Cytodifferentation of the cerebellum:
- External germinal layer -> marginal layer -> internal germinal layer
- IGL will produce deep nuclei, purkinje cells, and Golgi cells
- EGL will produce basket cells, granule cells, and stellate cells
- Radial Microbrain: severe microcephaly and will die in the first postnatal month because reduced number of cell units
- Microcephalia Vera: depletion of neurons in layers 2 and 3…reduced brain but normal gyral patterns…not a migratory defect
- Lissencephaly: anomaly characterized by a brain with poor or no sulci…migratory defect…4 layers instead of 6
- Polymicrogyria: too many abnormally small convolutions…layer 5 is fucked up…after 20th week and it is POSTMIGRATORY
- Heterotopias are collections of normal neurons in abnormal locations secondary to an arrest of radial migration of neurons…associated with schizophrenia…migration arrest mechanism is not understood
- Axon Formation, Guidance, and Elimination:
- Axon formation begins until neurons have arrived at their final destination
- Regulated by the growth cone -> important in the generation and guidance of axogenesis…interaction with specific molecules on cell membranes causes polymerization of actin filaments in the growth cone tip, causing growth of the cone in the specific direction of the interaction.
- Axon formation begins with microtubule polymerization within the cell body
- Path and guidance: adhesion molecules, nonpermissive substrates, and cell surface molecules which inhibit advancement of growth cones known as CONTACT INHIBITION
- Significant proportion of projection and commissural fibers are eliminated during development.
- Formation of synapses is a competitive process in that many more axons arrive at a target neuron than actually form synapses.
- The excess synapses are eliminated by a combination of events known as cell death, axonal pruning, and synaptic elimination.
- Final process in the development of the cerebral white matter is MYELINATION.
- Myelination occurs from caudal to rostral.
- The most common cause of cerebral white matter injury in infants is periventricular leukomalacia as a result of brain ischemia or hemorrhage in utero.
- Krabble disease is a buildup of toxic substance psychosine occurs within the oligodendrocyte resulting in cell death and subsequent loss of myelin.
- Callosal Agenenis is the absence of the commissure between the 2 hemispheres…fibers turn 90 degrees and course parallel to the interhemispheric fissure
- MOST of the growth of the brain takes place after birth….due to cell proliferation but MOSTLY myelination of fibers
- The immature brain contains more synapses than the mature brain…
- Myelination proceeds rapidly within the brain up to 2 yo…fibers associated with areas of the brain continue to myelinate well into the 3rd or 4th decade of life.
- Brain development differs in boys and girls:
- Boys have a larger globus pallidus and amygdala.
- Girls have a larger caudate and hippocampus
Tags: adenohypophysis, alar plate, basal plate, cauda equina, cerebellum, diencephalon, diencephalons, filum terminale, flocculonodular lobe, hippocampal commissure, hypoglossal nucleus, lumbar cistern, medulla, mesencephalon, metencephalon, midbrain, myelecephalon, nervous system development, neural crest cells, neural plate, neural tube, neurohypophysis, neurulation, notocord, nucleus ambiguous, oligodendrocytes, pituitary gland, pons, primitive meninx, rhombencephalon, schwann cells, subventricular zone, sulcus limitans, telencephalon
