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In Vivo Targeting of Neural Progenitor Cells in Ferret Neocortex by In Utero Electroporation
Published on: May 6, 2020
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YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex
Milos Kostic1, Judith T M L Paridaen1, Katherine R Long1
1Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Cell Reports
|April 25, 2019
Summary
The Hippo pathway
Area of Science:
- Neuroscience
- Developmental Biology
- Evolutionary Biology
Background:
- Neocortex expansion in mammals correlates with increased basal progenitor proliferation.
- The subventricular zone is a key area for progenitor activity.
Purpose of the Study:
- Investigate the role of YAP, a Hippo pathway effector, in basal progenitor proliferation.
- Determine YAP's contribution to neocortical evolution.
Main Methods:
- Compared YAP expression in basal progenitors across species with varying proliferative capacities (ferret, human, mouse).
- Utilized conditional gene expression in mice to activate YAP in basal progenitors.
- Employed pharmacological and genetic methods to inhibit YAP in ferret and human neocortex models.
Main Results:
- YAP expression and activity are high in highly proliferative ferret and human basal progenitors, but low in mouse basal progenitors.
- Constitutive YAP activation in mouse basal progenitors increased proliferation and upper-layer neuron production.
- YAP inhibition reduced cycling basal progenitor numbers in ferret and human developing neocortex.
Conclusions:
- YAP is both necessary and sufficient for promoting basal progenitor proliferation.
- Elevated YAP levels likely contributed to the evolutionary expansion of the mammalian neocortex.
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