PUBLICATION
Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis
- Authors
- Matsui, T., Thitamadee, S., Murata, T., Kakinuma, H., Nabetani, T., Hirabayashi, Y., Hirate, Y., Okamoto, H., and Bessho, Y.
- ID
- ZDB-PUB-110609-42
- Date
- 2011
- Source
- Proceedings of the National Academy of Sciences of the United States of America 108(24): 9881-6 (Journal)
- Registered Authors
- Hirate, Yoshikazu, Kakinuma, Hisaya, Matsui, Takaaki, Okamoto, Hitoshi
- Keywords
- left-right patterning, ciliogenesis
- MeSH Terms
-
- Animals
- Stem Cells/metabolism*
- In Situ Hybridization
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Fibroblast Growth Factor 8/genetics
- Fibroblast Growth Factor 8/metabolism*
- Signal Transduction*
- Animals, Genetically Modified
- Oligonucleotides, Antisense/genetics
- Organogenesis
- Gene Expression Regulation, Developmental
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Cadherins/genetics
- Cadherins/metabolism
- Body Patterning/genetics
- Feedback, Physiological
- Cell Adhesion
- Receptor, Fibroblast Growth Factor, Type 1/genetics
- Receptor, Fibroblast Growth Factor, Type 1/metabolism
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism*
- PubMed
- 21628557 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Matsui, T., Thitamadee, S., Murata, T., Kakinuma, H., Nabetani, T., Hirabayashi, Y., Hirate, Y., Okamoto, H., and Bessho, Y. (2011) Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis. Proceedings of the National Academy of Sciences of the United States of America. 108(24):9881-6.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping