Heparan sulphate proteoglycans (HSPGs) and chondroitin sulphate proteoglycans (CSPGs) are major components of the extracellular matrix (ECM),but whereas HSPGs regulate various developmental signalling pathways,including hedgehog (Hh) signalling, the function of CSPGs is less clear. In their study of mouse endochondral bone formation on , Nancy Schwartz and colleagues now demonstrate for the first time that CSPGs modulate Indian hedgehog (Ihh) signalling. The researchers show that chondroitin sulphate chains (CSCs) are under-sulphated in brachymorphic (bm)mutant mice, whereas heparan sulphate chains are normal. To investigate CSPG function, they analysed bm limb growth plates (tissue growth areas near the end of long bones), where they detected diminished Ihh signalling, an abnormal, aggregated distribution of Ihh, and decreased chondrocyte proliferation. Using biochemical assays, the authors show that Ihh binds CSCs directly; in addition, Ihh co-immunoprecipitates with the CSPG aggrecan. Based on these and other data, the researchers speculate that HSPGs and CSPGs can function together to establish morphogen gradients and thus modulate Hh signalling in the developing growth plate.
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