PUBLICATION

HSPG synthesis by zebrafish Ext2 and Extl3 is required for Fgf10 signalling during limb development

Authors

Norton, W.H., Ledin, J., Grandel, H., and Neumann, C.J.

ID

ZDB-PUB-051019-3

Date

2005

Source

Development (Cambridge, England) 132(22): 4963-4973 (Journal)

Registered Authors

Grandel, Heiner, Neumann, Carl J., Norton, Will

Keywords

Zebrafish, HSPG, Fgf10, Limb development, Ext, Heparan, Heparin

MeSH Terms

Fibroblast Growth Factor 10/deficiency
Fibroblast Growth Factor 10/genetics
Fibroblast Growth Factor 10/physiology*
Signal Transduction/genetics
Signal Transduction/physiology*
N-Acetylglucosaminyltransferases/physiology*
Heparan Sulfate Proteoglycans/biosynthesis*
Animals
Extremities/embryology*
Zebrafish/embryology*
Zebrafish/genetics
Phenotype
Zebrafish Proteins/genetics
Zebrafish Proteins/physiology
Mutation

(all 15)

PubMed

16221725 Full text @ Development

CTD

16221725

Abstract

Heparan sulphate proteoglycans (HSPGs) are known to be crucial for signalling by the secreted Wnt, Hedgehog, Bmp and Fgf proteins during invertebrate development. However, relatively little is known about their effect on developmental signalling in vertebrates. Here, we report the analysis of daedalus, a novel zebrafish pectoral fin mutant. Positional cloning identified fgf10 as the gene disrupted in daedalus. We find that fgf10 mutants strongly resemble zebrafish ext2 and extl3 mutants, which encode glycosyltransferases required for heparan sulphate biosynthesis. This suggests that HSPGs are crucial for Fgf10 signalling during limb development. Consistent with this proposal, we observe a strong genetic interaction between fgf10 and extl3 mutants. Furthermore, application of Fgf10 protein can rescue target gene activation in fgf10, but not in ext2 or extl3 mutants. By contrast, application of Fgf4 protein can activate target genes in both ext2 and extl3 mutants, indicating that ext2 and extl3 are differentially required for Fgf10, but not Fgf4, signalling during limb development. This reveals an unexpected specificity of HSPGs in regulating distinct vertebrate Fgfs.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bmp2b	fgf10a^tbvbo/tbvbo	standard conditions	Prim-25	pectoral fin	ISH	Fig. 3
bmp2b	fgf10a^tbvbo/tbvbo	standard conditions	Prim-5	pectoral fin bud	ISH	Fig. 3
bmp2b	WT	standard conditions	Prim-25	pectoral fin	ISH	Fig. 3
bmp2b	WT	standard conditions	Prim-5	pectoral fin bud	ISH	Fig. 3
dlx2a	ext2^tw25e/tw25e	standard conditions	Long-pec	pectoral fin	ISH	Fig. 6
dlx2a	extl3^tw24/tw24	standard conditions	Long-pec	pectoral fin	ISH	Fig. 6
dlx2a	fgf10a^tbvbo/tbvbo	standard conditions	Prim-25	pectoral fin	ISH	Fig. 3
dlx2a	fgf10a^tbvbo/tbvbo	standard conditions	Prim-5	pectoral fin bud	ISH	Fig. 3
dlx2a	WT	standard conditions	Prim-25	pectoral fin	ISH	Fig. 3
dlx2a	WT	standard conditions	Long-pec	pectoral fin	ISH	Fig. 6

1 - 10 of 62

Show

Phenotype

Mutations / Transgenics

Allele	Type	Affected Genomic Region
t24030	Point Mutation	fgf10a
tbvbo	Point Mutation	fgf10a
tw24	Point Mutation	extl3
tw25e	Point Mutation	ext2

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
fgf10a	MO1-fgf10a	MRPHLNO

Fish

Fish
ext2^tw25e/tw25e
extl3^tw24/tw24
fgf10a^{t24030/t24030}
fgf10a^tbvbo/tbvbo
WT

Antibodies

Orthology

Gene	Orthology
wnt7aa

Engineered Foreign Genes

Mapping

Entity Type	Entity Symbol	Location
Feature	tbvbo	Chr: 21 Details
GENE	fgf10a	Chr: 21 Details

Norton et al., 2005 ZDB-PUB-051019-3 PMID:16221725

HSPG synthesis by zebrafish Ext2 and Extl3 is required for Fgf10 signalling during limb development

Norton et al., 2005

ZDB-PUB-051019-3
PMID:16221725