MicroRNAs in early embryonic development : dissecting the role of miR-290 through miR-295 in the mouse

Abstract

MicroRNAs mediate developmental regulation of gene expression via translational repression of target mRNAs. Targeted deletion of the miRNA biogenesis machinery in the mouse has demonstrated essential roles for miRNAs during early development. In this thesis, I have examined the role of a family of miRNAs, miR-290 through miR-295 (miR-290 cluster), which are specifically expressed during early embryonic and germ cell development. This miRNA family is conserved only among mammals. miR-290 cluster miRNAs are transcribed and processed from a common capped and polyadenylated primary transcript in the mouse. Deletion of the miR-290 cluster in the mouse results in early embryonic lethality and misregulation of primordial germ cell migration, ultimately resulting in germ cell depletion, premature ovarian failure and infertility in the adult female. Loss of miR-290-295 mediated repression results in significant changes in the gene expression profile of embryonic stem cells, allowing for the accumulation and precocious expression of many developmental regulators involved in differentiation. As such, we have shown that the miR-290 cluster miRNAs are critical regulators of embryonic development.