Controlled Timelines of Gene Regulatory Networks (2024)

Undergraduate: Jason Menjivar-Hernandez

Faculty Advisor: Brian Kinney
Department: Biology

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Larval development in C. elegans entails four molting cycles during which crucial genetic and cellular processes must be precisely synchronized to facilitate shedding and regrowth of the cuticle enveloping the body. The core genes orchestrating this developmental timer drive the periodic expression of lin-4 miRNA throughout each molting cycle. In the larval skin, lin-4 expression is activated by Rev-Erb ortholog NHR-85 and ROR ortholog NHR-23; its expression is inactivated by lin-42 (Kinney et al. 2023). We set out to investigate how the timing of development is regulated in other tissues outside the larval skin, specifically the hermaphrodite gonad. Prior work implicates lin-42 upstream of the netrin receptor gene unc-5, which regulates the timing of DTC turning (Tennessen et al., 2006). lin-4 mutants have no vulvas, but the germline continues to grow. We found that lin-42 cycles in the DTC, but NHR-23 and NHR-85 do not. We searched for different factors with which LIN-42 might act to repress unc-5 by conducting a yeast 1-hybrid approach to find transcription factors that can bind the unc-5_x000D_
upstream regulatory region. After screening 672 genes, we found 7 hits that can bind the unc-5 regulatory region. The screen and in vivo validation will continue.