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Program in Molecular Medicine

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Biochemistry | Developmental Biology | Genetics | Genomics | Molecular Biology | Molecular Genetics


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 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 of and downstream from her-1 to prevent aberrantly activated male developmental programs in hermaphrodite embryos. Both of the predicted target genes that act downstream from the mir-35 family in this process, suppressor-26 (sup-26) and NHL (NCL-1, HT2A, and LIN-41 repeat) domain-containing-2 (nhl-2), encode RNA-binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway of Caenorhabditis elegans Repression of nhl-2 by the mir-35 family is required for not only proper sex determination but also viability, showing that a single microRNA target site can be essential. 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.


embryonic development, maternal control, microRNAs, mir-35–41, mir-35–42, sex determination

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© 2017 McJunkin and Ambros. Publisher PDF posted after 6 months as allowed by the publisher's author rights policy at

DOI of Published Version



McJunkin K, Ambros V. A microRNA family exerts maternal control on sex determination in C. elegans. Genes Dev. 2017 Feb 15;31(4):422-437. doi:10.1101/gad.290155.116. Epub 2017 Mar 9. PubMed PMID: 28279983; PubMed Central PMCID: PMC5358761. Link to article on publisher's website

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Genes and development

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Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License