title: Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis.
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.
authors.affiliation: Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Nara 630-0101, Japan. matsui@bs.naist.jp
authors.forename: Takaaki
authors.initials: T
authors.lastname: Matsui
authors.forename: Siripong
authors.initials: S
authors.lastname: Thitamadee
authors.forename: Tomoko
authors.initials: T
authors.lastname: Murata
authors.forename: Hisaya
authors.initials: H
authors.lastname: Kakinuma
authors.forename: Takuji
authors.initials: T
authors.lastname: Nabetani
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hirate
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Bessho
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D025461:Feedback, Physiological; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D038081:Organogenesis; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; C510076:Cnpy1 protein, zebrafish; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D051524:Fibroblast Growth Factor 8; D051496:Receptor, Fibroblast Growth Factor, Type 1