PT - JOURNAL ARTICLE AU - Katherine McJunkin AU - Victor Ambros TI - A microRNA family exerts maternal control on sex determination in <em>C. elegans</em> AID - 10.1101/083949 DP - 2016 Jan 01 TA - bioRxiv PG - 083949 4099 - http://biorxiv.org/content/early/2016/10/28/083949.short 4100 - http://biorxiv.org/content/early/2016/10/28/083949.full AB - Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally-contributed microRNAs may therefore play important roles in early development. We have elucidated a major biological role of the nematode mir-35 family of maternally-contributed, essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream and downstream of her-1 to prevent aberrantly activated male developmental programs in hermaphrodite embryos. The predicted target genes that act downstream of the mir-35 family in this process, sup-26 and nhl-2, both encode RNA binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway of C. elegans. Genome-wide profiling of SUP-26 binding targets reveals 775 mRNAs, most of which have no known role in sex determination, suggesting that the mir-35 family may modulate numerous other pathways via regulation of sup-26. Since sex determination in C. elegans requires zygotic gene expression to read the sex chromosome karyotype, early embryos must remain gender-naïve; our findings show that the mir-35 family microRNAs act in the early embryo to function as a developmental timer that preserves naïveté and prevents premature deleterious developmental decisions.