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February 2023

Radial glial cells (RGCs) are essential for the generation and organization of neurons in the cerebral cortex. They have an elongated bipolar morphology with basal and apical endfeet that reside in distinct niches, but how this subcellular compartmentalization of RGCs controls cortical development is largely unknown. Here, D'Arcy et al. generate the first subcellular proteome of RGCs and uncover new principles governing local control of cortical development. They discover a cohort of proteins that are significantly enriched in RGC basal endfeet, with MYH9 and MYH10 among the most abundant. Myh9 and Myh10 transcripts also localize to endfeet with distinct temporal dynamics. Although they each encode isoforms of non-muscle myosin II heavy chain, Myh9 and Myh10 have drastically different requirements for RGC integrity. Myh9 loss from RGCs decreases branching complexity and causes endfoot protrusion through the basement membrane. In contrast, Myh10 controls endfoot adhesion, as mutants have unattached apical and basal endfeet. The image shows radial glial basal endfeet (red) protruding through the basement membrane (grey) in the developing cortex of a Myh9 cKO mouse.

Image Credit: Brooke R. D'Arcy

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