Development of the Nervious System .txt

  1. Development of the Nervious System
    • During 3rd week of embryonic development: Ectoderm
    • on the dorsal surface of the embryo thickens to become the neural plate
    • This invaginates to form the neural groove, which continues to deepen.
    • The dorsal edges (neural folds) eventually fuse and the cylinder separates from the surface ectoderm to form the neural tube and neural crest
  2. Neural crest
    • gives rise to most of the
    • spinal
    • cranial nerve
    • autonomic ganglia: including neurons and supporting cells (schwann cells, meninges)
  3. The Neural Tube
    • becomes the CNS:
    • Cranial portion: becomes the brain
    • Caudal portion: becomes the spinal cord
    • Cavity: becomes the ventricles and central canal of spinal cord
  4. Developmental disorders
    • result from failure of the neural tube to close or separate from surface ectoderm
    • rostral defects cause anencephaly, caudal defects cause spina bifida
    • Defects vary in severity from a few defective vertebral arches (10% of population) to the CNS being an open pit continuous with the body surface
  5. Overview of changes in Neural Tube During Development: weeks 4-36
    • Neural tube expands in size and develops several bends near its anterior end
    • Cerebral hemispheres show the greatest expansion and cover the rest of the brain.
  6. Early changes in neural tube weeks 4-8
    • the neural tube develops three primary compartments (vesicles) and bends by week 4
    • these further develop into 5 secondary compartments by week 6
    • which will form the 5 major brain divisions
  7. Proencephalon
    • telencephalon
    • diencephalon
  8. Telencephalon
    • cerebral hemispheres
    • lateral ventricle
  9. Diencephalon
    • Dorsal Thalamus and Epi, Hypo, Sub Thalamus
    • Visual system
    • Pituitary 3rd ventricle
  10. Mesencephalon
    • Midbrain
    • Cerebral aqueduct
  11. Rhomboencephalon
    • Metencephalon
    • Myelencephalon
  12. metencephalon
    • pons
    • cerebellum
    • rostral half of 4th ventricle
  13. Myelencephalon
    • medulla
    • caudal half of 4th ventricle
  14. dorsal half of the neural tube form the ALAR PLATE
    • where sensory neurons develop
    • This becomes the dorsal horn
  15. Ventral half of the neural tube
    Basal plate: will give rise to motor neurons of the ventral horn
  16. In the spinal chord the ventral and dorsal horns form the butterfly
    • In the brain stem:
    • the alar plate migrates laterally
    • basal plate migrates dorsally
    • so that sensory and motor nuclei lie lateral medial to each other.
  17. Nerve cells are influenced by molecular signals
    • Nerve cell growth involves extension of axons and dendrites from the cell body
    • pathfinding: to targets, and
    • Subsequent synaptogenesis: with targets
    • These events are essential for development of normal structure and connectivity
    • They are controlled by precisely timed changes in gene expression and molecular signaling
    • Growth of axons and dendrites occurs at their tips, where specialized, motile structures occur known as growth cones
  18. Growth factors
    • embryonic nerve cells depend on growth factors for their survival
    • Many target tissues secrete growth factors
    • The bind to receptors on nerve terminals, become internalized, and are retrogradely transported to the cell body where they alter gene expression
    • Released by neurons, target tissues, glia, non-neural cells (fibroblasts, macrophages, muscle, etc.)
    • Each population of nerve cells depends on specific type of growth factors.
    • Many growth factors continue to be synthesized in the ADUKT brain, adult neurons apparently not as dependent on growth factors for their survival, but other important properties may be regulated (synaptic function, sprouting of terminals)
    • Major Questions: are neurodegenerative disease caused by decreased secretion of growth factors
  19. Extracellular Matrix (ECM)
    • molecules provide an adhesive substrate for growing nerve fibers
    • examples: collagens, fibronectin, laminins
  20. Cell adhesion Molecules:
    • (CAMs) on cell membranes cause adhesion and fasciculation
    • Examples: NCAM, L1, cadherins (Ca++ dependent)
  21. Signals that guide nerve fibers
    are not recognized also to be important in guiding the growth ob flood vessels to establish the vascular pattern for the body!
  22. Development of the cerebral hemispheres and cortex: weeks 8-36
    • Adult cerebral hemispheres: cell bodies are located in a thin region of the outer cortex (gray matter), axons are located deeper in a fiber layer (white matter), and some nuclei (cell bodies) are buried deep in the fiber layer
    • Cortex is layered based on the types and positions of nerve cell bodies with regional differences: neocortex has 6 layers.
  23. Embryonic brain
    is composed of thin telencephalic compartments containing scattered cells surrounding the internal space that will become the ventricles
  24. The hemispheres development
    • they develop by proliferation and migration of neuroblasts in the wall of the embryonic telencephalic vesicles. This process
    • 1) increases the mass of the telencephalic compartments
    • 2) allows neurons to migrate towards the pial surface where they form the cortex
    • 3) results in the formation of cortical layers for information processing
  25. Neuroepithelial cells proliferate in a zone (subventricular zone) adjacent to the lateral ventricle of the telencephalic vesicle.
    Cell bodies of differentiating neurons migrate toward the pial surface either on their own or along fivers of radial glial cells that span the width between ventricle and pial surface
  26. Subventricular zone
    • remains an important area in some regions of the adult brain where neuronal stem cells continue to form neurons even in adults.
    • These areas have potential for harvesting stem cells for use in repairing damaged areas of the brain
  27. Neuronal proliferation and migration results in thickening of telencephalic compartment, outer cortex of cell bodies, and inner fiber layer.
  28. As proliferation and migration proceed, telencephalic vesicles
    grow forward, upward and backward in a "C" shaped path covering subcortical structures
  29. Local differences in rate of proliferation
    cause gyri, sulci, and fissures between weeks 14 and 32
  30. Defects in proliferation and migration cause abnormalities such as
    • nicrocephaly
    • polymicrogyria or macrogyria
    • lissencephaly - smooth cortex lacking gyri and sulci
    • Heterotropias - misplaced gray matter
    • schizencephaly - clefts in hemisphere
    • Abnormal development of the corpus callosum (communication between hemispheres)
  31. Threats to Normal Prenatal Development
    • Teratogens are environmental substances that can impair fetal development
    • The timing, amount of exposure, and sensitivity of organs to these substances determines the magnitude of defects
    • Compounds such as alcohol, thalidomide (sedative), anti-seizure drugs, retinoic acid (accutane) and other substances are known to alter early CNS development
  32. Normal CNS development also depends on maternal thyroid hormone and iodine which cross the placenta
    Maternal hypothyroidism or iodine deficiency result in CRETINISM (mental retardation and other physical defects)
  33. Post natal CNS development occurs over a long time course, at least until the end of the teen years
    • In fact, development more appropriately can be considered over the span of a lifetime
    • The brain triples in weight and reaches 3/4 adult size during the first 2 years!!
  34. 3 Types of postnatal changes within the CNS:
    • 1) myelination: most axons require this to conduct action potentials; the infant CNS is not fully functional until myelination of pathways has occurred
    • 2) Dendritic growth and pruning: growth and retraction of dendrites are dynamic processes that are influenced by levels of activity in neural circuits
    • 3) Synapse formation: communication between neurons: this is a dynamic process in which connections between neurons are strengthened or weakened based on activity
  35. Environmental stimulation has a major impact on all 3 of the above processes
    • the growth/pruning of dendrites and the subsequent formation/loss of synaptic connections are controlled to a large extent by the use/disuse ofcircuits in the brain.
    • This provides a fantastic capacity for communication between nerve cells
    • They rely on experience - and early experience has great implications for later functional capabilities of the CNS
  36. Dangers of Lead: the earlier years are particularly sensitive to some toxic substances that can alter CNS function permanently
    heavy metal compounds such as lead can cause irreversible CNS damage and it is a constant threat to children who may ingest lead from their environment
  37. Critical Periods
    • Experiments with sensory systems have shown that their normal function in adults requires appropriate sensory stimulation at certain critical times during development
    • These critical periods are times when neuronal circuit are capable of dendritic and synaptic reorganization that establishes their capacity to process information
    • Sensitive periods - also are recognized as opportune times in postnatal development that can influence, but not completely determine, functional capabilities in the mature brain stem
    • The concept of critical/sensitive periods probably extends to many CNS systems because of the role of experience in the postnatal processes that control CNS maturation
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Development of the Nervious System .txt