The Role of MicroRNAs in Vertebrate Ectodermal Specification

在脊椎动物胚胎的发育过程中，外胚层细胞在两种发育途径中进行选择：一种导致神经系统的形成，而另一种产生表皮。这项研究调查了microRNAs的作用，这些小RNA分子可以抑制其他基因的表达，在这些细胞成为神经或表皮命运的过程中。MicroRNAs被认为在胚胎发育和成人组织正常功能的基因表达控制中发挥重要作用；它们与干细胞向特定细胞类型的分化以及许多形式的癌症和其他人类疾病有关。然而，它们在神经发育起始中的具体功能尚不清楚。这些实验验证了一种已知的特定microRNA的作用假设，该microRNA限制对表皮承托至关重要的基因的表达，以及microRNA在新承托的神经细胞和表皮外胚层之间的表达如何不同。此外，这些研究将确定新形成的神经外胚层和表皮外胚层中受microrna调控的基因；计算方法将用于鉴定靶向这些基因的候选microrna。这些结果将揭示中枢神经系统形成的分子机制，并确立microrna在胚胎发育中的新作用。他们还将促进基于干细胞的神经疾病或损伤治疗的发展。此外，这些研究将为本科生和研究生提供机会，接受分子生物学和生物信息学以及脊椎动物发育生物学的研究训练。

During the development of vertebrate embryos, ectoderm cells choose between two developmental pathways: one leads to the formation of the nervous system, while the other produces the epidermis. This study investigates the role of microRNAs, small RNA molecules that can inhibit the expression of other genes, in the process by which these cells become committed to neural or epidermal fates. MicroRNAs are thought to play important roles in the control of gene expression both in embryonic development and the normal functions of adult tissues; they have been implicated in the differentiation of stem cells into specific cell types, as well as in many forms of cancer and other human diseases. Their specific functions in the initiation of neural development, however, are unknown. These experiments test hypotheses on the role of a specific microRNA known to restrict expression of a gene critical to epidermal commitment and on how the expression of microRNAs may differ between newly committed neural or epidermal ectoderm. In addition, these studies will identify genes that are regulated by microRNAs in newly committed neural ectoderm and epidermal ectoderm; computational methods will be used to identify candidate microRNAs that target these genes. These results will reveal molecular mechanisms that underlie the formation of the central nervous system, and establish new roles for microRNAs in embryonic development. They will also contribute to the development of stem cell-based therapies for neurological disease or injury. In addition, these studies will provide opportunities for undergraduate and graduate students to receive research training in molecular biology and bioinformatics, as well as vertebrate developmental biology.