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bioRxiv · 10.1101/2022.11.17.517002

Target of Rapamycin Complex 2 modulates development through Hedgehog/Patched signaling in C. elegans

Emans, S. W.·Yerevanian, A.·Ahsan, F.·Zhou, Y.·Cedillo, L.·Soukas, A. A.
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Abstract

Both Hedgehog (Hh) signaling and target of rapamycin complex 2 (TORC2) are central, evolutionarily conserved pathways that regulate development and metabolism. In C. elegans, loss of essential TORC2 component RICTOR (rict-1) causes delayed development, shortened lifespan, reduced brood, small size, and increased fat. Here we report that knockdown of Hedgehog-related morphogen grd-1 and its Patched-related receptor ptr-11 rescues delayed development in TORC2 loss of function mutants, indicating an unexpected role for grd-1/ptr-11 in slowing developmental rate downstream of nutrient sensing pathways. Further, we implicate chronic stress transcription factor pqm-1 as a key transcriptional effector of grd-1/ptr-11 in slowing whole-organism growth. We propose that the TORC2/grd-1/ptr-11/pqm-1 signaling relay acts as a critical executor of growth to slow development when C. elegans encounters unfavorable growth conditions. Summary statementDevelopmental rate in C. elegans is dramatically slowed in animals deficient in nutrient-sensitive target of rapamycin complex 2 signaling and slowing is effected by increased activity of a previously uncharacterized Hh-r/Ptr signaling relay.

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Emans, S. W., Yerevanian, A., Ahsan, F., Zhou, Y., Cedillo, L., Soukas, A. A.. 2022-11-18. Target of Rapamycin Complex 2 modulates development through Hedgehog/Patched signaling in C. elegans. https://doi.org/10.1101/2022.11.17.517002

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