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

• MDGA1 is an IgCAM required for aggregation of basal progenitors (BPs) in the SVZ
• MDGA1 complexes with the gap junction protein Connexin43 in BP cell membranes
• MDGA1 deficiency leads to reduced size and proliferation of the SVZ and ectopic BPs
• MDGA1 deficiency leads to reduced production of cortical layer neurons

SummaryThe 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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