Heparan sulphate proteoglycans (HSPGs) are complex molecules that are critically important for signalling by secreted molecules during development. Despite this, pinning down their individual roles in development has proved a challenge. Norton and colleagues now report that the exostosins Ext2 and Extl3, which synthesise the HS sidechains of HSPG, are required for Fgf signalling during zebrafish development (see p. 4963). The researchers show that fgf10 is disrupted in deadalus, a zebrafish pectoral fin mutant that closely resembles ext2 and extl3 mutants. They report that while Fgf10 rescues target gene expression in fgf10 mutants, it does not do so in ext2 or extl3 mutants, indicating that HSPG synthesis is needed for Fgf10 signalling. The rescue of ext2 and extl3 mutants by Fgf4 revealed an unexpected specificity of HSPGs in regulating vertebrate Fgfs. On p. 5055, Stickens et al. report that Ext2-null mouse embryos fail to gastrulate, while Ext2+/– mice develop ectopic bony growths, providing further insights into Ext2's role in vertebrate development.

©2005.
2005