The majority of the skeletal elements, except the flat bones of the skull, are formed by endochondral ossification, in which cartilage is replaced by bone. The formation of cartilage is a multi-step process termed chondrogenesis, during which undifferentiated mesenchymal cells condense and undergo differentiation towards chondrocytes. Notwithstanding recent advances, our knowledge of the detailed mechanisms implicated in cartilage and bone formation is still scarce. Recent genetic, cellular and biochemical studies have highlighted the importance of TGFβ signaling and the activity of the transcription factor Sox9 during the early stages of vertebrate limb chondrogenesis.
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We apologize for the many original references that cannot be cited within the limitations of this review. We want to acknowledge Dr. Masanao Tsuda for discussions and May Schwartz for help in the preparation of this manuscript. JRL is supported by a grant from Instituto de Salud Carlos III Health Institute. Work in our laboratories is supported by the Cellex and G. Harold and Leila Y. Mathers Charitable Foundations, the Health Ministries of Spain and Catalonia, and the NIH.