Epithelial effects on limb chondrogenesis involve extracellular matrix and cell shape

Collagen gel cultures of limb bud mesenchymal cells are normally permissive for chondrogenesis but become inhibitory for chondrogenesis when they are preconditioned by limb ectoderm. This inhibition is specific for cartilage differentiation, inasmuch as myoblast differentiation is unaffected and flattened, fibroblastic cells are more numerous on conditioned gels. The antichondrogenic effect of ectoderm-conditioned gels is not blocked by agents that elevate intracellular cyclic AMP levels and that promote chondrogenesis under other conditions. In contrast, the inhibitory effect of the ectoderm is alleviated when cultures are treated with cytochalasin D, a cytoskeleton-disrupting agent that causes the cells to remain spherical. These results suggest that ectoderm-conditioned collagen gels inhibit chondrogenesis through an effect on cell shape.