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Title: Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis
Authors: Matsui, Takaaki
Thitamadee, Siripong
Murata, Tomoko
Kakinuma, Hisaya
Nabetani, Takuji
Hirabayashi, Yoshio
Hirate, Yoshikazu
Okamoto, Hitoshi
Bessho, Yasumasa
Keywords: Cell cluster formation
Left-right patterning
Positive feedback loop
Issue Date: 14-Jun-2011
Publisher: National Academy of Science
Volume: 108
Issue: 24
Start page: 9881
End page: 9886
Abstract: The assembly of progenitor cells is a crucial step for organ formation during vertebrate development. Kupffer’s vesicle (KV) is a key organ required for the left-right asymmetric body plan in zebrafish, and is generated from a cluster of approximately 20 dorsal forerunner cells (DFCs). Although several genes are known to be involved in KV formation, how DFC clustering is regulated and how cluster formation then contributes to KV formation remain unclear. Here we show that positive feedback regulation of FGF signaling by Canopy1 (Cnpy1) controls DFC clustering without affecting DFC specification and DFC number. Cnpy1 positively regulates FGF signals within DFCs, which in turn promotes Cadherin1-mediated cell adhesion between adjacent DFCs to sustain cell cluster formation. When this FGF positive feedback loop is disrupted, the DFC cluster fails to form, eventually leading to KV malformation and defects in the establishment of laterality. Our results therefore uncover both a previously unidentified role of FGF signaling during vertebrate organogenesis and a regulatory mechanism underlying cell cluster formation, which is an indispensable step for formation of a functional KV and establishment of the left-right asymmetric body plan.
ISSN: 0027-8424
Rights: Copyright (c) 2011 by the National Academy of Sciences
Text Version: author
Publisher DOI: 10.1073/pnas.1017248108
Appears in Collections:バイオサイエンス研究科 / Graduate School of Biological Sciences

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