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YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway
Yi-Ting Lin1, Jing-Ya Ding, Ming-Yang Li
1Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
Experimental Cell Research
|June 5, 2012
Summary
The Hippo pathway
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Cell number regulation is crucial for development.
- The Hippo pathway and signaling cascades like Sonic Hedgehog (Shh) influence cell proliferation and differentiation.
- The interplay between Hippo and other pathways in neuronal differentiation is not fully understood.
Purpose of the Study:
- To investigate the role of YAP, a Hippo pathway component, in neuronal differentiation.
- To explore the relationship between YAP and the Shh signaling pathway during neuronal differentiation.
- To elucidate the mechanism by which YAP regulates neuronal differentiation in mouse models.
Main Methods:
- Utilized P19 cells, a mouse embryonic carcinoma cell line, as a model system.
- Induced neuronal differentiation by expressing the Ascl1 gene.
- Manipulated YAP expression and utilized knockdown of Gli2, a Shh pathway transcription factor.
Main Results:
- YAP overexpression promoted cell proliferation and inhibited neuronal differentiation.
- YAP activated Shh signaling, evidenced by increased Patched homolog 1 (Ptch1) expression.
- Knockdown of Gli2 rescued the neuronal differentiation defect caused by YAP overexpression in both P19 cells and primary cortical progenitors.
Conclusions:
- YAP inhibits neuronal differentiation.
- Shh signaling acts downstream of YAP in the regulation of neuronal differentiation.
- Targeting the YAP-Shh axis offers a potential strategy for controlling neuronal differentiation.
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