MICROREGULATION OF ZEBRAFISH SKELETAL SYSTEM DEVELOPME~T BY MICRORNAS

MicroRNAs are small regulatory RNAs that control various developmental and physiological processes in animals and plants. To study the involvement of microRNAs in skeletal development, I manipulated the expression of miR-140, which is strongly expressed in the developing skeleton, and miR-196, which is located among the body patterning Hox cluster genes. I found that miR-140 regulates zebrafish palate formation by interfering with neural crest cell migration through the inhibition of the expression of the platelet derived growth factor receptor alpha (pdgfra) gene. I also found that miR-196 regulates zebrafish pectoral fin initiation by regulating the expression of the retinoic acid receptor alpha b (rarab) gene and that miR-196 is involved in the patterning of zebrafish pharyngeal arches and vertebrae. These results illuminate previously unknown regulatory mechanisms of skeletal development. I also reviewed current knowledge concerning microRNAs in skeletal development and evolution and discussed potential v relationships between microRNAs and skeletal disease