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Published 27 September 2004. doi:10.1083/jcb.200403110
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 7, 975-981
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STAT3 noncell-autonomously controls planar cell polarity during zebrafish convergence and extension

Chiemi Miyagi1, Susumu Yamashita1,2, Yusuke Ohba3,4, Hisayoshi Yoshizaki3, Michiyuki Matsuda3, and Toshio Hirano1,2,5

1 Department of Molecular Oncology, Graduate School of Medicine
2 Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences
3 Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
4 Information and Cell Function, PRESTO, JST, Saitama 332-0012, Japan
5 Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan

Address correspondence to Toshio Hirano, Dept. of Molecular Oncology (C7), Graduate School of Medicine, Osaka University, 2-2, Yamada-oka Suita, Osaka 565-0871, Japan. Tel.: 81-6-6879-3880. Fax: 81-6-6879-3889. email: hirano{at}molonc.med.osaka-u.ac.jp


Abstract
Zebrafish signal transducer and activator of transcription 3 (STAT3) controls the cell movements during gastrulation. Here, we show that noncell-autonomous activity of STAT3 signaling in gastrula organizer cells controls the polarity of neighboring cells through Dishevelled-RhoA signaling in the Wnt-planar cell polarity (Wnt-PCP) pathway. In STAT3-depleted embryos, although all the known molecules in the Wnt-PCP pathway were expressed normally, the RhoA activity in lateral mesendodermal cells was down-regulated, resulting in severe cell polarization defects in convergence and extension movements identical to Strabismus-depleted embryos. Cell-autonomous activation of Wnt-PCP signaling by {Delta}N-dishevelled rescued the defect in cell elongation, but not the orientation of lateral mesendodermal cells in STAT3-depleted embryos. The defect in the orientation could be rescued by transplantation of shield cells having noncell-autonomous activity of STAT3 signaling. These results suggest that the cells undergoing convergence and extension movement may sense the gradient of signaling molecules, which are expressed in gastrula organizer by STAT3 and noncell-autonomously activate PCP signaling in neighboring cells during zebrafish gastrulation.

Key Words: STAT3; Dishevelled; Rho; planar cell polarity; zebrafish


Abbreviations used in this paper: FRET, fluorescence resonance energy transfer; MO, morpholino oligonucleotide; PCP, planar cell polarity; STAT, signal transducer and activator of transcription.


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