Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation.
The mechanisms that control cell proliferation and cell differentiation during morphogenesis of the endochondral skeleton of vertebrates are poorly understood. Indian hedgehog (Ihh) signaling from prehypertrophic chondrocytes has been implicated in the control of chondrocyte maturation by way of feedback control of a second secreted factor parathyroid hormone-related peptide (PTHrP) at the articular surfaces. Analysis of an Ihh null mutant suggests a more extensive role for Ihh in skeletal development. Mutants display markedly reduced chondrocyte proliferation, maturation of chondrocytes at inappropriate position, and a failure of osteoblast development in endochondral bones. Together, the results suggest a model in which Ihh coordinates diverse aspects of skeletal morphogenesis through PTHrP-dependent and independent processes.
St-Jacques
B
B
Harvard University, Department of Molecular and Cellular Biology, Cambridge, Massachusetts 02138 USA.
Hammerschmidt
M
M
McMahon
A P
AP
D000483:Alleles; D000818:Animals; D002356:Cartilage / Q000166:cytology; D002454:Cell Differentiation; D002455:Cell Division; D019902:Chondrocytes / Q000166:cytology*; D017353:Gene Deletion; D053823:Hedgehog Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators
D053823:Hedgehog Proteins; D011506:Proteins; D015534:Trans-Activators