~BN03 CNS Development.ppt

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  • TGF: activates protein kinases SHH: motor neurons
  • ~BN03 CNS Development.ppt

    1. 1. Development of the Nervous System Lecture 3
    2. 2. Development of the Brain <ul><li>Adult brain structure product of… </li></ul><ul><ul><li>Genetic instructions </li></ul></ul><ul><ul><li>Cell-to-cell signals </li></ul></ul><ul><ul><li>Interaction b/n child and external world </li></ul></ul><ul><li>Early development </li></ul><ul><ul><li>Before synaptogenesis </li></ul></ul><ul><ul><li>Activity-independent </li></ul></ul><ul><ul><li>Critical periods ~ </li></ul></ul>
    3. 3. Gastrulation & Neuralation <ul><li>Gastrulation </li></ul><ul><ul><li>Invagination of embryo </li></ul></ul><ul><ul><li>single sheet of cells  3 cell layers </li></ul></ul><ul><ul><li>Formation of notocord </li></ul></ul><ul><li>Neuralation </li></ul><ul><ul><li>Induction signals from notocord… </li></ul></ul><ul><ul><li>To neuroectoderm </li></ul></ul><ul><ul><li>Growth of neural precursor cells~ </li></ul></ul>
    4. 4. Neural Induction <ul><li>Induction signals </li></ul><ul><ul><li>From embryonic tissue </li></ul></ul><ul><ul><li>Modulate gene expression </li></ul></ul><ul><li>Retinoic acid </li></ul><ul><ul><li>Steroid hormone </li></ul></ul><ul><li>Peptide hormones </li></ul><ul><ul><li>Fibroblast growth factor (FGF) </li></ul></ul><ul><ul><li>Transforming growth factor (TGF) </li></ul></ul><ul><ul><li>Sonic hedge hog (shh) ~ </li></ul></ul>
    5. 5. Retinoic Acid – Jekyl & Hyde? <ul><li>Vitamin A derivative </li></ul><ul><ul><li>Too little  abnormal development </li></ul></ul><ul><ul><li>Too much  abnormal development </li></ul></ul><ul><li>Inductive signal </li></ul><ul><ul><li>Critical period </li></ul></ul><ul><ul><li>Localization ~ </li></ul></ul>
    6. 6. Embryological Origin <ul><li>Embryo has 3 layers </li></ul><ul><ul><li>endoderm </li></ul></ul><ul><ul><ul><li>internal organs </li></ul></ul></ul><ul><ul><li>mesoderm </li></ul></ul><ul><ul><ul><li>muscles & skeleton </li></ul></ul></ul><ul><ul><li>ectoderm </li></ul></ul><ul><ul><ul><li>nervous system & skin ~ </li></ul></ul></ul>
    7. 7. Embryological Origin <ul><li>About 3 weeks </li></ul><ul><ul><li>Neural plate forms </li></ul></ul><ul><ul><li>sheet of cells </li></ul></ul><ul><li>Neural groove </li></ul><ul><ul><li>folds rostral to caudal will form tube ~ </li></ul></ul>
    8. 8. Development of N.S. <ul><li>Neural tube </li></ul><ul><ul><li>CNS develops from walls </li></ul></ul><ul><ul><ul><li>spina bifida - caudal tube fails to close </li></ul></ul></ul><ul><ul><li>as tube develops dorsal portion pinches off & forms...~ </li></ul></ul>
    9. 9. Development of N.S. <ul><li>Neural crest </li></ul><ul><ul><li>develops into all neurons of PNS </li></ul></ul><ul><li>Mesoderm </li></ul><ul><ul><li>somites ---> vertebrae & muscles ~ </li></ul></ul>
    10. 10. Differentiation <ul><li>Specialization of structures </li></ul><ul><li>3 primary vesicles </li></ul><ul><ul><li>rostral end of tube </li></ul></ul><ul><ul><li>develops into brain </li></ul></ul><ul><li>Prosencephalon  forebrain </li></ul><ul><li>Mesencephalon  midbrain </li></ul><ul><li>Rhombencephalon  hindbrain ~ </li></ul>
    11. 11. Prosencephalon <ul><li>Secondary vesicles </li></ul><ul><ul><li>form & separate </li></ul></ul><ul><ul><li>optic  retinas </li></ul></ul><ul><ul><ul><li>retina & optic nerve CNS </li></ul></ul></ul><ul><ul><ul><li>not PNS </li></ul></ul></ul><ul><ul><li>telencephalic  telencephalon </li></ul></ul><ul><ul><li>remainder  diencephalon ~ </li></ul></ul>
    12. 12. Other Primary Vesicles <ul><li>Mesencephalic  mesencephalon </li></ul><ul><ul><li>dorsal - tectum </li></ul></ul><ul><ul><li>ventral - tegmentum </li></ul></ul><ul><ul><li>tube - cerebral aqueduct </li></ul></ul><ul><li>Rhombencephalic </li></ul><ul><ul><li>rostral - metencephalon </li></ul></ul><ul><ul><li>caudal - myelencephalon </li></ul></ul><ul><ul><li>tube - 4th ventricle ~ </li></ul></ul>
    13. 13. Neural Tube Defects: Rostral <ul><li>Neural tube fails to close </li></ul><ul><li>anencephaly </li></ul><ul><ul><li>skull & brain partially or totally absent </li></ul></ul><ul><ul><li>perinatal mortality </li></ul></ul><ul><li>Encephalocele </li></ul><ul><ul><li>parts of brain protrude outside skull </li></ul></ul><ul><ul><li>mental disability depends on extent ~ </li></ul></ul>
    14. 14. Neural Tube Defects: Caudal <ul><li>Spina Bifida </li></ul><ul><ul><li>Cleft spine </li></ul></ul><ul><ul><li>neural tube fails to close </li></ul></ul><ul><li>Incidence </li></ul><ul><ul><li>Spina bifida occulta </li></ul></ul><ul><ul><ul><li>40% of Americans </li></ul></ul></ul><ul><ul><li>Spina Bifida Manifesta </li></ul></ul><ul><ul><ul><li>1 in a 1000 births ~ </li></ul></ul></ul>
    15. 15. Spina Bifida Manifesta <ul><li>Meningocele (4%) </li></ul><ul><ul><li>fluid-filled meningeal cyst </li></ul></ul><ul><ul><li>protrudes through unfused vertebral arches </li></ul></ul><ul><ul><li>SC/nerves not in sac </li></ul></ul><ul><ul><li>repaired surgically </li></ul></ul><ul><ul><li>less severe disability than myelomeningocele ~ </li></ul></ul>
    16. 16. Spina Bifida Manifesta <ul><li>Myelomeningocele (96%) </li></ul><ul><ul><li>protruding cyst as with meningocele </li></ul></ul><ul><ul><li>spinal cord / nerves in protruding sac </li></ul></ul><ul><li>Effects </li></ul><ul><ul><li>paralysis, incontinence, learning disabilities </li></ul></ul><ul><ul><li>70-90% also hydrocephalus </li></ul></ul><ul><ul><ul><li>can cause severe brain damage </li></ul></ul></ul><ul><ul><li>Repaired surgically ~ </li></ul></ul>
    17. 17. Neural Tube Defects: Prevention <ul><li>Possible genetic component </li></ul><ul><ul><li>reoccurrence in families </li></ul></ul><ul><ul><li>ethnic/racial relationship </li></ul></ul><ul><li>Folic Acid (Folate) Deficiency </li></ul><ul><ul><li>50-70% of cases preventable </li></ul></ul><ul><ul><li>CDC guidelines </li></ul></ul><ul><ul><li>not planning pregnancy: 400  g/day </li></ul></ul><ul><ul><li>planned pregnancy: 4000  g/day </li></ul></ul><ul><ul><ul><li>under direction of health care provider ~ </li></ul></ul></ul>

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