RRC ID 65581
Author Matsui T, Thitamadee S, Murata T, Kakinuma H, Nabetani T, Hirabayashi Y, Hirate Y, Okamoto H, Bessho Y.
Title Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis.
Journal Proc Natl Acad Sci U S A
Abstract The assembly of progenitor cells is a crucial step for organ formation during vertebrate development. Kupffer's vesicle (KV), a key organ required for the left-right asymmetric body plan in zebrafish, is generated from a cluster of ~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. Cnpy1 positively regulates FGF signals within DFCs, which in turn promote 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.
Volume 108(24)
Pages 9881-6
Published 2011-6-14
DOI 10.1073/pnas.1017248108
PII 1017248108
PMID 21628557
PMC PMC3116425
MeSH Animals Animals, Genetically Modified Body Patterning / genetics Cadherins / genetics Cadherins / metabolism Cell Adhesion Embryo, Nonmammalian / cytology Embryo, Nonmammalian / embryology Embryo, Nonmammalian / metabolism Feedback, Physiological Fibroblast Growth Factor 8 / genetics Fibroblast Growth Factor 8 / metabolism* Gene Expression Regulation, Developmental Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism In Situ Hybridization Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Oligonucleotides, Antisense / genetics Organogenesis Receptor, Fibroblast Growth Factor, Type 1 / genetics Receptor, Fibroblast Growth Factor, Type 1 / metabolism Signal Transduction* Stem Cells / metabolism* Zebrafish / embryology Zebrafish / genetics Zebrafish / metabolism* Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 9.412
Zebrafish RIKEN WT