The growth and evolutionary expansion of the cerebral cortex are defined by the spatial-temporal production of neurons, which itself depends on the decision of radial glial cells (RGCs) to self-amplify or to switch to neurogenic divisions. The mechanisms regulating these RGC fate decisions are still incompletely understood. Here we describe a novel and evolutionarily conserved role of the canonical BMP transcription factors SMAD1/5 in controlling neurogenesis and growth during corticogenesis. Reducing the expression of both SMAD1 and SMAD5 in neural progenitors at early mouse cortical development caused microcephaly and an increased production of early-born cortical neurons at the expense of late-born ones, which correlated with the premature differentiation and depletion of the pool of cortical progenitors. Gain- and loss-of-function experiments performed during early cortical neurogenesis in the chick revealed that SMAD1/5 activity supports self-amplifying RGC divisions and restrain the neurogenic ones. Furthermore, we demonstrate that SMAD1/5 stimulate RGC self-amplification through the positive post-transcriptional regulation of the Hippo signaling effector YAP. We anticipate this SMAD1/5-YAP signaling module to be fundamental in controlling growth and evolution of the amniote cerebral cortex.
A SMAD1/5-YAP signaling module drives radial glia self-amplification and growth of the developing cerebral cortex
These authors contributed equally to the work.
Present address: Helmholtz Zentrum Muenchen, Institute of Stem Cell Research, Biomedical Center, Grosshaderner Strasse 9, 82152 Planegg-Martinsried, Germany
Currently Viewing Accepted Manuscript - Newer Version Available
Sonia Najas, Isabel Pijuan, Anna Esteve-Codina, Susana Usieto, Juan D. Martinez, An Zwijsen, Maria L. Arbonés, Elisa Martí, Gwenvael Le Dréau; A SMAD1/5-YAP signaling module drives radial glia self-amplification and growth of the developing cerebral cortex. Development 2020; dev.187005. doi: https://doi.org/10.1242/dev.187005
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