The developing limb is a useful model for studies on the mechanisms involved in tissue patterning during development. This proposal is concerned with the processes that lead to the differentiation of cartilage elements in their proper spacial relationships in the developing avian and mouse limb. By means of grafting studies in ovo and tissue culture studies, the dynamics and inductive properties of the limb ectoderm will be examined. An ectodermally derived factor that inhibits cartilage differentiation will be characterized. By use of a high density culture system in which chondrogenesis occurs, the mechanism by which specific interactions between mesenchymal cells promote chondrogenesis will be analyzed. Particular attention will be placed on extracellular matrix receptors and changes in the organization of the actin cytoskeleton in the initiation of chondrogenesis. Studies will also be concerned with the nature of a precartilage extracellular matrix molecule and its role in chondrogenesis. The role of insulin-like growth factor I in chondrogenesis and in mediating defects in chondrogenesis in the droopy ear mouse mutant model will be studied in cell cultures by use of blocking antibody to IGF-I and molecular probes. Finally, the mechanism by which cell shape changes modulate the expression of cartilage specific genes will be examined. Particular attention will be placed on translation level regulation of the synthesis of various collagen types.
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