GRD-1/PTR-11, the C. elegans hedgehog/patched-like morphogen-receptor pair, modulates developmental rate

Area of Science:

• Developmental Biology
• Molecular Signaling Pathways
• Genetics

Background:

• Hedgehog (Hh) and target of rapamycin complex 2 (TORC2) are evolutionarily conserved signaling pathways crucial for development and metabolism.
• Loss of TORC2 function in C. elegans (rict-1 mutants) results in delayed development, reduced lifespan, smaller size, and increased fat accumulation.

Purpose of the Study:

• To investigate the interaction between Hh and TORC2 signaling pathways in regulating developmental rate.
• To identify molecular players involved in TORC2-mediated control of organismal growth.

Main Methods:

• RNA interference (RNAi) for gene knockdown (grd-1, ptr-11).
• Overexpression studies of Hh pathway components (grd-1, ptr-11).
• Analysis of developmental timing and organismal growth in C. elegans.
• Identification of transcriptional effectors using genetic approaches.

Main Results:

• Knockdown of hedgehog-related morphogen grd-1 and its receptor ptr-11 rescues delayed development in TORC2 loss-of-function mutants.
• Overexpression of grd-1 and ptr-11 significantly delays wild-type development, mirroring TORC2 loss-of-function phenotypes.
• The transcription factor pqm-1 is identified as a key effector mediating the growth-slowing effects of grd-1 and ptr-11.

Conclusions:

• Hedgehog pathway components grd-1 and ptr-11 play an unexpected role in slowing developmental rate, potentially downstream of nutrient-sensing pathways.
• TORC2, grd-1, and ptr-11 signaling converge on the transcription factor pqm-1 to regulate organismal development and growth.
• This study uncovers a novel link between Hh signaling and nutrient-sensing pathways in controlling developmental timing.