miR199a/214簇在斑马鱼咽软骨发育过程中的功能研究

MicroRNAs (miRNAs) have a critical role in controlling fundamental cellular functions and developmental processes. Some miRNAs have been found to be implicated in chondrogenes and paly an important role in craniofacial cartilage development and craniofacial malformation. Our preliminary studies showed that miR199a/214 cluster encodes three miRNAs (miR199a-5p, miR199a-3p and miR214), which are all expressed in zebrafish pharynageal arches at late developmental stage. Inactivation of miR199a-5p and miR214, leading to impair ceratobranchial development, the morphants showed reduction of ceratobranchial and cells arrangement disorder, while miR214 knockdown does not affect the pharyngeal cartilage development, indicating that miR199a/214 cluster may be implicated in pharyngeal cartilage development. In this study, we will explore the founction of miR199a/214 cluster in pharyngeal cartilage development, analysis the molecular mechanism of the expression of miR199a/214 cluster, and find out the target genes. We will have all understanding of the mechanism of cartilage development and craniofacial malformation.

MicroRNAs个体发育和生理病理过程中发挥重要作用。研究表明在软骨发生系统中表达多种miRNAs，这些miRNAs有可能在软骨发生过程中起重要作用，与软骨发育疾病相关。我们的前期研究结果表明，miR199a/214簇的miR199a-5p、miR199a-3p和miR214在斑马鱼胚胎发育的晚期，均在咽区表达。采用morpholino分别抑制这三个miRNA的活性时，发现miR199a-5p和miR214的敲低均会导致斑马鱼角腮骨变小，细胞排列稀疏，而敲低miR199a-3p，斑马鱼咽部软骨发育正常。因此，miR199a/214簇可能在斑马鱼咽软骨发育过程中起重要作用。本项目拟深入研究miR199a/214簇在咽软骨的发育过程中的功能，分析调控 miR199a/214簇表达的分子机制，并寻找出miR199a/214簇的目标靶基因。旨在探索咽软骨发生及相关疾病的分子机理。