Functional Analysis of microRNAs in C. elegans spermatogenesis

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7. PROJECT SUMMARY The production of functional gametes is of central importance to the survival of all sexually reproducing species. Our goal is to identify the microRNAs that function to control the essential process of spermatogenesis in C. elegans. microRNAs are indispensable regulators of gene expression that are required for animal development and physiology. microRNAs have been found to be misregulated in patients with male factor infertility as well as in testicular germ cell tumors. However, the specific pathways and targets regulated by individual microRNAs in the process of spermatogenesis remain largely unknown. The study of microRNAs in C. elegans has been instrumental in defining the core principles of individual microRNA regulation of targets in developmental pathways. This work will provide new insights into the principles of microRNA function in regulatory networks that function in the process of spermatogenesis. microRNAs are required for mammalian spermatogenesis but their role in C. elegans spermatogenesis remains uncharacterized. This work will address three central questions: 1) What specific events of spermatogenesis require microRNAs? 2) What individual microRNAs function are expressed in the male gonad and function to regulate spermatogenesis? and 3) What pathways and direct targets are regulated the mir-44 family of microRNAs? This work will identify specific defects in spermatogenesis, pathways, and direct targets regulated by the mir-44 family. This work will provide a resource for future investigation to comprehensively define the functions of the subset of microRNAs that act in the male germ line to regulate the process of spermatogenesis.