Spatial Activation of TORC1 Is Regulated by Hedgehog and E2F1 Signaling in the Drosophila Eye

Area of Science:

• Developmental Biology
• Cell Signaling
• Molecular Biology

Background:

• Target of rapamycin complex 1 (TORC1) is a key regulator of cell growth, responding to nutrients and growth factors.
• TORC1 signaling is well-understood at the cellular level, but its regulation in multicellular tissues remains largely unknown.
• The developing Drosophila eye provides a model system to study tissue-specific signaling during development.

Purpose of the Study:

• To investigate the regulation of TORC1 signaling in multicellular tissues during development.
• To identify the specific developmental events and signaling pathways that control TORC1 activity in the Drosophila eye.
• To elucidate the role of TORC1 in cell-cycle progression during tissue development.

Main Methods:

• Utilized the developing Drosophila eye as a model organism.
• Investigated TORC1 activation during the second mitotic wave (SMW), a terminal synchronous cell division.
• Examined the interplay between Hedgehog (Hh) signaling, E2F1, cyclin D/Cdk4 complex, and TORC1 activity.

Main Results:

• TORC1 is selectively activated in the SMW of the developing Drosophila eye.
• Hedgehog (Hh) signaling regulates TORC1 via E2F1 and the cyclin D/Cdk4 complex, independent of insulin and amino acid pathways.
• TORC1 activation is crucial for the G1/S cell-cycle transition and can rescue cell-cycle defects in Hh-deficient cells.

Conclusions:

• Hedgehog signaling spatially regulates TORC1 activity during tissue development in multicellular organisms.
• This Hh-dependent regulation of TORC1 is evolutionarily conserved.
• TORC1 plays a critical role in coordinating cell growth with developmental cell divisions.