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Title: YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

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 thatmore » 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. -- Highlights: Black-Right-Pointing-Pointer YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. Black-Right-Pointing-Pointer YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the Yap-overexpression phenotype in P19 cells. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the Yap-overexpression phenotype in cortical progenitors.« less

Authors:
;  [1];  [2];  [3];  [2];  [1];  [4]
  1. Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan (China)
  2. Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan (China)
  3. Department of Anatomy and Cell Biology, National Yang-Ming University, Taipei 112, Taiwan (China)
  4. (China)
Publication Date:
OSTI Identifier:
22212596
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 318; Journal Issue: 15; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CARCINOMAS; CELL PROLIFERATION; DROSOPHILA; MICE; NERVE CELLS; NERVOUS SYSTEM; PHENOTYPE; TRANSCRIPTION FACTORS

Citation Formats

Lin, Yi-Ting, Ding, Jing-Ya, Li, Ming-Yang, Yeh, Tien-Shun, Wang, Tsu-Wei, E-mail: twwang@ntnu.edu.tw, Yu, Jenn-Yah, E-mail: jyyu@ym.edu.tw, and Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan. YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway. United States: N. p., 2012. Web. doi:10.1016/J.YEXCR.2012.05.005.
Lin, Yi-Ting, Ding, Jing-Ya, Li, Ming-Yang, Yeh, Tien-Shun, Wang, Tsu-Wei, E-mail: twwang@ntnu.edu.tw, Yu, Jenn-Yah, E-mail: jyyu@ym.edu.tw, & Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan. YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway. United States. doi:10.1016/J.YEXCR.2012.05.005.
Lin, Yi-Ting, Ding, Jing-Ya, Li, Ming-Yang, Yeh, Tien-Shun, Wang, Tsu-Wei, E-mail: twwang@ntnu.edu.tw, Yu, Jenn-Yah, E-mail: jyyu@ym.edu.tw, and Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan. Mon . "YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway". United States. doi:10.1016/J.YEXCR.2012.05.005.
@article{osti_22212596,
title = {YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway},
author = {Lin, Yi-Ting and Ding, Jing-Ya and Li, Ming-Yang and Yeh, Tien-Shun and Wang, Tsu-Wei, E-mail: twwang@ntnu.edu.tw and Yu, Jenn-Yah, E-mail: jyyu@ym.edu.tw and Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan},
abstractNote = {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. -- Highlights: Black-Right-Pointing-Pointer YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. Black-Right-Pointing-Pointer YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the Yap-overexpression phenotype in P19 cells. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the Yap-overexpression phenotype in cortical progenitors.},
doi = {10.1016/J.YEXCR.2012.05.005},
journal = {Experimental Cell Research},
number = 15,
volume = 318,
place = {United States},
year = {Mon Sep 10 00:00:00 EDT 2012},
month = {Mon Sep 10 00:00:00 EDT 2012}
}