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YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex.

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Kostic,  Milos
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Paridaen,  Judith
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/cone/persons/resource/persons221457

Kalebic,  Nereo
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/cone/persons/resource/persons219479

Namba,  Takashi
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/cone/persons/resource/persons219252

Huttner,  Wieland
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Kostic, M., Paridaen, J., Long, K. S., Kalebic, N., Langen, B., Grübling, N., et al. (2019). YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex. Cell reports, 27(4), 1103-1118. doi:10.1016/j.celrep.2019.03.091.


Cite as: https://hdl.handle.net/21.11116/0000-0006-7E7A-5
Abstract
Neocortex expansion during mammalian evolution has been linked to an increase in proliferation of basal progenitors in the subventricular zone. Here, we explored a potential role of YAP, the major downstream effector of the Hippo pathway, in proliferation of basal progenitors. YAP expression and activity are high in ferret and human basal progenitors, which exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. Conditional expression of a constitutively active YAP in mouse basal progenitors resulted in increased proliferation of basal progenitor and promoted production of upper-layer neurons. Pharmacological and genetic interference with YAP function in ferret and human developing neocortex resulted in decreased abundance of cycling basal progenitors. Together, our data indicate that YAP is necessary and sufficient to promote the proliferation of basal progenitors and suggest that increases in YAP levels and presumably activity contributed to the evolutionary expansion of the neocortex.