First published online April 24, 2009
Development 136, 1005e (2009)
© The Company of Biologists Limited
Sulphated proteoglycans meshing to the bone?
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
p. 1697, 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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Related articles in Development:
- Sulfation of chondroitin sulfate proteoglycans is necessary for proper Indian hedgehog signaling in the developing growth plate
- Mauricio Cortes, Alexis T. Baria, and Nancy B. Schwartz
Development 2009 136: 1697-1706.
[Abstract]
[Full Text]