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

Abstract

ABSTRACTBoth Hedgehog (Hh) signaling and target of rapamycin complex 2 (TORC2) are central, evolutionarily conserved pathways that regulate development and metabolism. InC. 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 morphogengrd-1and its Patched-related receptorptr-11rescues delayed development in TORC2 loss of function mutants, indicating an unexpected role forgrd-1/ptr-11in slowing developmental rate downstream of nutrient sensing pathways. Further, we implicate chronic stress transcription factorpqm-1as a key transcriptional effector ofgrd-1/ptr-11in slowing whole-organism growth. We propose that the TORC2/grd-1/ptr-11/pqm-1signaling relay acts as a critical executor of growth to slow development whenC. elegansencounters unfavorable growth conditions.Summary statementDevelopmental rate inC. elegansis 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.