Multiple Dose-Dependent Effects ofLis1on Cerebral Cortical Development

• DOI: 10.1523/jneurosci.23-05-01719.2003
• Publication Date: 2018-04-04T20:45:28Z
• Authors: Michael J. Gambello; Dawn L. Darling; Jessica Yingling; Teruyuki Tanaka; Joseph G. Gleeson; Anthony Wynshaw-B...
• Keywords: Subplate; Neuroblast; Neocortex

Humans with heterozygous inactivating mutations of the Lis1 gene display type I lissencephaly, a severe form cortical dysplasia hypothesized to result from abnormal neuronal migration. Previously we reported construction an allelic series in mice analyze effects graded reduction LIS1 protein on pathogenesis this disorder and demonstrated cell autonomous defect migration (Hirotsune et al., 1998). Here report systematic examination consequences dosage neocortical development using wild-type, null (45% protein), compound null/hypomorphic (35% protein) mice. The preplate, Cajal-Retzius cells, radial glial scaffold appeared unaffected by levels. However, dose-dependent morphologic change disorganization subplate was noted. defects were found vivo vitro. position number mitotic cells ventricular zone more as levels decreased, suggesting interkinetic nuclear neuroblast proliferation. progressive thinning cortex occurred programmed death. Thus, addition its requirement for migration, influences generation survival neuroblasts. These studies reveal importance orderly cerebral morphogenesis suggest new insights into lissencephaly.