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

Cell Adhesion
Zebrafish/embryology
Zebrafish/genetics
Zebrafish/metabolism*
Receptor, Fibroblast Growth Factor, Type 1/genetics
Receptor, Fibroblast Growth Factor, Type 1/metabolism
Fibroblast Growth Factor 8/genetics
Fibroblast Growth Factor 8/metabolism*
Body Patterning/genetics
Embryo, Nonmammalian/cytology
Embryo, Nonmammalian/embryology
Embryo, Nonmammalian/metabolism
Oligonucleotides, Antisense/genetics
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Stem Cells/metabolism*
Feedback, Physiological
Signal Transduction*
Gene Expression Regulation, Developmental
Animals, Genetically Modified
Animals
Nerve Tissue Proteins/genetics
Nerve Tissue Proteins/metabolism*
Cadherins/genetics
Cadherins/metabolism
Green Fluorescent Proteins/genetics
Green Fluorescent Proteins/metabolism
In Situ Hybridization
Organogenesis

(all 29)

PubMed

21628557 Full text @ Proc. Natl. Acad. Sci. USA

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

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
cdh1	WT	control	Shield	forerunner cell group	ISH	Fig. 5
cdh1	WT + MO1-cnpy1	standard conditions	Shield	forerunner cell group	ISH	Fig. 5
cnpy1	WT	standard conditions	75%-epiboly	forerunner cell group	ISH	Fig. S1
cnpy1	WT	chemical treatment: SU5402	Shield	forerunner cell group	ISH	Fig. 1
cnpy1	WT	control	Shield	forerunner cell group	ISH	Fig. 1
cnpy1	WT	standard conditions	75%-epiboly	margin	ISH	Fig. S1
cnpy1	WT	standard conditions	5-9 somites	midbrain hindbrain boundary neural rod	ISH	Fig. S1
cnpy1	WT	standard conditions	5-9 somites	polster	ISH	Fig. S1
cnpy1	WT	standard conditions	5-9 somites	tail bud	ISH	Fig. S1
dand5	WT	standard conditions	5-9 somites	Kupffer's vesicle	ISH	Fig. S6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-cnpy1	standard conditions	Shield	cell-cell adhesion mediated by cadherin decreased process quality, abnormal	Fig. 5
WT + MO1-cnpy1	standard conditions	Shield	endodermal cell mislocalised, abnormal	Fig. 1
WT + MO1-cnpy1	standard conditions	Shield	forerunner cell group distributed, abnormal	Fig. 1
WT + MO1-cnpy1	standard conditions	Shield	forerunner cell group distributed, abnormal	Fig. 5
WT + MO1-cnpy1	standard conditions	75%-epiboly	cell-cell adhesion mediated by cadherin decreased process quality, abnormal	Fig. 5
WT + MO1-cnpy1	standard conditions	75%-epiboly	forerunner cell group distributed, abnormal	Fig. 5
WT + MO1-cnpy1	standard conditions	5-9 somites	cilium assembly decreased process quality, abnormal	Fig. 2
WT + MO1-cnpy1	standard conditions	5-9 somites	Kupffer's vesicle cilium decreased amount, abnormal	Fig. 2
WT + MO1-cnpy1	standard conditions	5-9 somites	Kupffer's vesicle cilium decreased length, abnormal	Fig. 2
WT + MO1-cnpy1	standard conditions	5-9 somites	Kupffer's vesicle development decreased process quality, abnormal	Fig. 2

1 - 10 of 20

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ha01Tg	Tg(-5.0sox17:EGFP)	Transgenic Insertion
ti282a		Point Mutation	fgf8a

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cdh1	MO2-cdh1	MRPHLNO
cnpy1	MO1-cnpy1	MRPHLNO
fgf8a	MO3-fgf8a	MRPHLNO
tbx16	MO3-tbx16	MRPHLNO

Fish

Fish
fgf8a^{ti282a/ti282a}
ha01Tg
ha01Tg + MO1-cnpy1
WT
WT + MO1-cnpy1
WT + MO3-fgf8a

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Matsui et al., 2011 ZDB-PUB-110609-42 PMID:21628557

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

Matsui et al., 2011

ZDB-PUB-110609-42
PMID:21628557