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
-
- Animals
- Extremities/embryology*
- Fibroblast Growth Factor 10/deficiency
- Fibroblast Growth Factor 10/genetics
- Fibroblast Growth Factor 10/physiology*
- Heparan Sulfate Proteoglycans/biosynthesis*
- Mutation
- N-Acetylglucosaminyltransferases/physiology*
- Phenotype
- Signal Transduction/genetics
- Signal Transduction/physiology*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology
- PubMed
- 16221725 Full text @ Development
- CTD
- 16221725
Citation
Norton, W.H., Ledin, J., Grandel, H., and Neumann, C.J. (2005) HSPG synthesis by zebrafish Ext2 and Extl3 is required for Fgf10 signalling during limb development. Development (Cambridge, England). 132(22):4963-4973.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping