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A SMAD1/5-YAP signaling module drives radial glial cell expansion and growth of the developing cerebral cortex

View ORCID ProfileSonia Najas, Isabel Pijuan, Anna Esteve-Codina, Susana Usieto, Juan D. Martinez, An Zwijsen, Mariona L. Arbonés, Elisa Martí, View ORCID ProfileGwenvael Le Dréau
doi: https://doi.org/10.1101/558486
Sonia Najas
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri Reixac 10-15, 08028 Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain
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Isabel Pijuan
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri Reixac 10-15, 08028 Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain
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Anna Esteve-Codina
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, 08028 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain
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Susana Usieto
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri Reixac 10-15, 08028 Barcelona, Spain
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Juan D. Martinez
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri Reixac 10-15, 08028 Barcelona, Spain
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An Zwijsen
Department of Cardiovascular Sciences, KU Leuven, Leuven 3000, Belgium
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Mariona L. Arbonés
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri Reixac 10-15, 08028 Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain
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Elisa Martí
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri Reixac 10-15, 08028 Barcelona, Spain
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Gwenvael Le Dréau
Department of Developmental Biology, Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, C/ Baldiri Reixac 10-15, 08028 Barcelona, Spain
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  • ORCID record for Gwenvael Le Dréau
  • For correspondence: gldbmc@ibmb.csic.es
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Summary

Cerebral cortex expansion in development and evolution is defined by the spatiotemporal production of neurons. Although the intracellular mechanisms regulating the decision of radial glial cells (RGCs) to self-amplify or produce neurons are beginning to be deciphered, the upstream signalling pathways involved are less well understood. Here we highlight an evolutionarily conserved role of the canonical BMP pathway in controlling neurogenesis and growth during corticogenesis. Through gain- and loss-of-function experiments on chick embryos, we found that the activity of the BMP effectors SMAD1/5 supports RGC self-amplification and impedes their premature differentiation and exhaustion. The microcephaly and overall growth retardation observed in conditional Smad1/5wt/fl;Nestin:Cre+/0 (SmadNes) mutant mice reveal this role to be evolutionarily conserved. Furthermore, we demonstrate that the effect of SMAD1/5 on RGCs depends on the activity 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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 14, 2019.
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A SMAD1/5-YAP signaling module drives radial glial cell expansion and growth of the developing cerebral cortex
Sonia Najas, Isabel Pijuan, Anna Esteve-Codina, Susana Usieto, Juan D. Martinez, An Zwijsen, Mariona L. Arbonés, Elisa Martí, Gwenvael Le Dréau
bioRxiv 558486; doi: https://doi.org/10.1101/558486
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A SMAD1/5-YAP signaling module drives radial glial cell expansion and growth of the developing cerebral cortex
Sonia Najas, Isabel Pijuan, Anna Esteve-Codina, Susana Usieto, Juan D. Martinez, An Zwijsen, Mariona L. Arbonés, Elisa Martí, Gwenvael Le Dréau
bioRxiv 558486; doi: https://doi.org/10.1101/558486

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