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Integrin-associated protein(IAP)is known to be involved in neurite differentiation in cultured neurons,but the function of IAP in brain development is largely unknown.We determined that IAP mRNA was robustly expressed in the developing cerebellum,and the expression of IAP mRNA and protein was highly correlated with the development of granule cells.In mice at postnatal day 10,IAP protein was poorly expressed in the outer layer of external granule layer(EGL)(oEGL),where granule cells actively proliferate; by comparison,IAP was expressed strongly in the inner layer of EGL(iEGL),where granule cells become postmitotic.IAP knockout mice at P8 showed an increase in the number of proliferating granule cells in the oEGL and a reduction in the number of postmitotic granule cells in the iEGL.Knocking out the IAP gene impaired the radial migration of granule cells from the EGL to IGL and blocking the function of IAP lowered the number of migrating granule cells in slice and explant cultures.In primary granule cells,knocking out IAP resulted in a reduction in the number of axonal collaterals and dendritic branches; by contrast,overexpressing and activating IAP increased axonal length and the numbers of axonal collaterals and dendritic branches.Furthermore,the length of the fissure between Lobules VI and VII was decreased in IAP knockout mice at P21 and at 14 wk after birth.Lastly,IAP knockout mice exhibited increased social interaction at P21 and depressive-like behaviors at 10 wk after birth.Taken together,our results provide evidence that IAP regulates granule cell proliferation,migration,and neurite differentiation during the development of the cerebellum.Our results also imply that aberrations of IAP might be risk factors that cause abnormalities in cerebellar development and the atypical behaviors associated with these abnormalities.