The Role of MicroRNAs in Vertebrate Ectodermal Specification

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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.