Formation of the Cortical Subventricular Zone Requires MDGA1-Mediated Aggregation of Basal Progenitors

Cell Reports
Carlos G Perez-Garcia, Dennis D M O'Leary

Abstract

The subventricular zone (SVZ) provides a specialized neurogenic microenvironment for proliferation and aggregation of basal progenitors (BPs). Our study reveals a mechanism for the aggregation of BPs within the SVZ required for their proliferation and generation of cortical layer neurons. The autism-related IgCAM, MDGA1, is locally expressed in the BP cell membrane where it co-localizes and complexes with the gap junction protein Connexin43. To address MDGA1 function, we created a floxed allele of MDGA1 and deleted it from BPs. MDGA1 deletion results in reduced BP proliferation and size of the SVZ, with an aberrant population of BPs ectopically positioned in the cortical plate. These defects are manifested in diminished production of cortical layer neurons and a significant reduction of the cortical layers. We conclude that MDGA1 functions to aggregate and maintain BPs within the SVZ providing the neurogenic niche required for their proliferation and generation of cortical layer neurons.

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Citations

Feb 24, 2016·Frontiers in Cellular Neuroscience·Francesco PetrelliPaola Bezzi
Mar 19, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Veronica D'AnnunzioJuan J Poderoso
Sep 13, 2017·FEBS Letters·Subashika Govindan, Denis Jabaudon

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