The Role of mir-290-295 in Murine Embryonic and Germ Cell Development

MicroRNAs, 22nt long RNAs derived from hairpin transcripts, are important regulators of gene expression and have been shown to participate in regulation of every biological process known to date. Mir-290 through mir-295 (mir-290-295) is a mammalian-specific miRNA cluster that, in the mouse, is expressed specifically in early embryos and embryonic germ cells. This thesis examines the in vivo consequences of targeted deletion of mir-290-295 in the developing mouse embryo. Mir-290-295 deficiency results in a partially penetrant embryonic lethality. Mir-290-295 is not required for early preimplantation development but is instead required for later postimplantation development. In surviving mir-290-295 deficient embryos, female but not male fertility is compromised. This impairment in fertility arises from a defect in migrating primordial germ cells and occurs equally in male and female mutant animals. Male mir-290-295-mice, due to the extended proliferative lifespan of their germ cells, are able to recover from this initial germ cell loss and are fertile. Female mir-290-295-/mice are unable to recover and are sterile due to premature ovarian failure. Thesis Supervisor: Rudolf Jaenisch Title: Professor of Biology