Subcellular proteome of radial glia reveals non-muscle myosins control basal endfeet to mediate interneuron organization

Abstract

AbstractRadial glial cells (RGCs) are essential for the generation and organization of neurons in the cerebral cortex. RGCs have an elongated bipolar morphology with basal and apical endfeet which reside in distinct niches. Yet, how this subcellular compartmentalization of RGCs controls cortical development is largely unknown. Here, we employin vivoproximity labeling using unfused BirA to generate the first subcellular proteome of RGCs and uncover new principles governing local control of cortical development. We discover a cohort of proteins that are significantly enriched in RGC basal endfeet, with MYH9 and MYH10 among the most abundant.Myh9andMyh10transcripts also localize to endfeet with distinct temporal dynamics. Although they each encode isoforms of non-muscle myosin II heavy chain,Myh9andMyh10have drastically different requirements for RGC integrity.Myh9loss from RGCs decreases branching complexity and causes endfoot protrusion through the basement membrane. In contrast,Myh10controls endfoot adhesion, as mutants have unattached apical and basal endfeet. Finally, we show thatMyh9- andMyh10-mediated regulation of RGC complexity and endfoot position non-cell autonomously controls interneuron number and organization in the marginal zone. Our study demonstrates the utility ofin vivoproximity labeling for dissecting local control of complex systems, and reveals new mechanisms for dictating RGC integrity and cortical architecture.