Studies on the Molecular Mechanisms of Cartilage Pattern Formation in Chick Limb Bud

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To elucidate the molecular mechanisms of cartilage pattern formation of chick limb bud, retinoic acid (RA), which was known to induce limb duplication, was locally applied to the various regions of the limb bud or added to the limb mesodermal cells in culture. RA applied to the antero-distal region of the limb bud induced ZPA activity and stimulated the expression of RARbeta mRNA. The induction of ZPA activity was independently of duplicate formation and depended on the presence of AER at the distal top of the limb bud.RA induced the formation of 18kD protein in limb bud cell culture. This induction occurred only in the cells of anterior and distal region. Induction of ZPA activity in cell culture also occurred only in these cells, suggesting the role of 18kD protein in ZPA induction.RA promotes the proliferation and chondrogenesis in cultured distal mesodermal cells of limb bud. This promotion also occurred in the cells of antero-distal region.These results suggest a common mechanism in the induction of ZPA activity in vivo and in vitro and the promotion of cell proliferation and chondrogenesis by RA. .