MARCKS Controls Distribution Of Cajal-Retzius Cells In Neocortex Development

During the development of the mammalian cerebral cortex,newborn neurons undergo radial migration from the ventricular zone toward the surface of the cortical plate to form an highly ordered lamina structure.Cajal-Retzius?CR?cells have been suggested to be crucial for the lamination of the mammalian cerebral cortex by controlling the migration of new born neurons via the release of reelin.However,molecular mechanisms that control regular distribution of CR cells in the marginal zone?MZ?remain elusive.We find that myristoylated alanine-rich C Kinase substrate?MARCKS?is highly expressed in CR cells of mice during early prenatal development.Interestingly,crossing Marcks ^floxp/floxp(Marcks^f/f)mice with Nestin-Cre mice,we find that conditional knockout?cKO?of Marcks gene in neural progenitors formation of many CR cell-free gaps,which were usually accompanied by neuronal ectopia composed of deep layer neurons traversing through the outer layer of the developing cortex.By coincidence,the end-feets of radial progenitor cells failed to anchor to the MZ regions devoid of CR cells.To investigate whether the gap between CR cells is a cell-autonomous effect when Marcks conditionally knock out in Marcks^f/f;Nestin-Cre mice.We then specifically knock out Marcks in a subpopulation of CR cells.We find that more than forty percent Marcks^f/f;Dbx1-Cre mice with gaps between CR cells.Meanwhile,we specifically knock out Marcks in VZ/SVZ progenitors by virtue of in utero electroporation.Results showed that the integrity of CR cells layer is not disrupted by Marcks knockout in VZ/SVZ neuronal progenitors.Taken together,this study indicates that MARCKS can regulate the integrity of CR cells in in the MZ,and eventually affect the lamination and overall architecture of the normal development of the neocortex.