TORC2 signaling antagonizes SKN-1 to induce C. elegans mesendodermal embryonic development

Area of Science:

• Cell Biology
• Developmental Biology
• Genetics

Background:

• The target of rapamycin (TOR) kinase is a conserved regulator of cell growth and metabolism.
• TOR functions in two complexes, TORC1 and TORC2, with TORC2 and Rictor recently linked to aging and metabolism.
• SKN-1 is a transcription factor crucial for mesendoderm development, cellular homeostasis, and longevity.

Purpose of the Study:

• To investigate the role of rict-1/Rictor, a component of TORC2, in embryonic development.
• To determine if TORC2 regulates the function of the transcription factor SKN-1 during embryogenesis.

Main Methods:

• Genetic inactivation of rict-1 and other TOR components in C. elegans.
• Analysis of mesendodermal specification in SKN-1 deficient embryos.
• Investigating the downstream effects of rict-1/TORC2 using SGK-1 gain-of-function mutants.

Main Results:

• Genetic inactivation of rict-1/Rictor suppressed lethality in SKN-1 deficient embryos.
• This suppression was associated with restored mesendodermal precursor specification, leading to intestine and pharynx formation.
• Inactivation of other TORC2 components, but not TORC1, also partially rescued SKN-1 embryonic lethality.
• The SGK-1 kinase was identified as a downstream mediator of rict-1/TORC2 function.

Conclusions:

• TORC2, acting through Rictor and SGK-1, antagonizes SKN-1 during C. elegans embryonic development.
• This pathway is critical for proper mesendodermal specification and embryonic viability.
• The findings reveal a novel regulatory interaction between TORC2 and SKN-1 in controlling developmental processes.