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A SMAD1/5-YAP signalling module drives radial glia self-amplification and growth of the developing cerebral cortex

AuthorsNajas, Sònia; Pijuan, Isabel; Esteve-Codina, Anna; Susana Usieto; Martínez, Juan D. ; Zwijsen, An; Arbones, Maria L. CSIC ORCID ; Martí, Elisa CSIC ORCID ; Dréau, G. le CSIC ORCID
KeywordsCerebral cortex
Radial glial cells
Bone morphogenetic proteins (BMPs)
SMAD transcription factors
Issue Date2020
PublisherCompany of Biologists
CitationDevelopment 147: dev187005 (2020)
AbstractThe 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 restrains the neurogenic ones. Furthermore, we demonstrate that SMAD1/5 stimulate RGC self-amplification through the positive post-transcriptional regulation of the Hippo signalling effector YAP. We anticipate this SMAD1/5-YAP signalling module to be fundamental in controlling growth and evolution of the amniote cerebral cortex.
Publisher version (URL)http://dx.doi.org/10.1242/dev.187005
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