YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

Yi Ting Lin, Jing Ya Ding, Ming Yang Li, Tien Shun Yeh, Tsu Wei Wang, Jenn Yah Yu

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model to study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation.

Original languageEnglish
Pages (from-to)1877-1888
Number of pages12
JournalExperimental Cell Research
Volume318
Issue number15
DOIs
Publication statusPublished - 2012 Sep 10

Fingerprint

Hedgehogs
Cell Proliferation
Basic Helix-Loop-Helix Transcription Factors
Organ Size
Nervous System
Drosophila
Cell Differentiation
Transcription Factors
Cell Count
Apoptosis
Carcinoma
Neurons
Cell Line
Growth
Genes

Keywords

  • Cortical progenitor
  • Hippo pathway
  • Neuronal differentiation
  • P19 cell
  • Sonic hedgehog
  • YAP

ASJC Scopus subject areas

  • Cell Biology

Cite this

YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway. / Lin, Yi Ting; Ding, Jing Ya; Li, Ming Yang; Yeh, Tien Shun; Wang, Tsu Wei; Yu, Jenn Yah.

In: Experimental Cell Research, Vol. 318, No. 15, 10.09.2012, p. 1877-1888.

Research output: Contribution to journalArticle

Lin, Yi Ting ; Ding, Jing Ya ; Li, Ming Yang ; Yeh, Tien Shun ; Wang, Tsu Wei ; Yu, Jenn Yah. / YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway. In: Experimental Cell Research. 2012 ; Vol. 318, No. 15. pp. 1877-1888.
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