1. A SMAD1/5-YAP signalling module drives radial glia selfamplification and growth of the developing cerebral cortex.
- Author
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Najas, Sonia, Pijuan, Isabel, Esteve-Codina, Anna, Usieto, Susana, Martinez, Juan D., Zwijsen, An, Arbone's, Maria L., Martı', Elisa, and Le Dre'au, Gwenvael
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CEREBRAL cortex ,NEUROGLIA ,DEVELOPMENTAL neurobiology ,BONE morphogenetic proteins ,TRANSCRIPTION factors ,NEURAL stem cells - Abstract
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 restrains the neurogenic ones. Furthermore, we demonstrate that SMAD1/5 stimulate RGC self-amplification through the positive posttranscriptional 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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