Distinct signaling of Drosophila Activin/TGF-beta family members

Area of Science:

• Cellular signaling pathways
• Developmental biology
• Molecular mechanisms of growth

Background:

• Transforming growth factor-beta (TGF-β) family ligands signal via type I/II receptor complexes.
• Receptor activation leads to SMAD transcription factor phosphorylation.
• Understanding ligand-specific signaling is crucial for deciphering developmental processes.

Purpose of the Study:

• To investigate which TGF-β family members signal through the Drosophila type I receptor BABO.
• To identify ligands that mediate growth via the BABO receptor complex.
• To elucidate the downstream signaling events and functional outcomes of BABO activation.

Main Methods:

• Analysis of signaling pathways for all seven TGF-β family members in Drosophila.
• Utilizing activated forms of SMAD2 and MAD for gain-of-function studies.
• Investigating ligand-receptor interactions involving BABO and PUNT.
• Phenotypic analysis of mutant Drosophila, including dawdle (daw) mutants.

Main Results:

• Drosophila Activin (dACT) and Dawdle (DAW) activate dSMAD2 through BABO and PUNT.
• BABO activation can also phosphorylate the BMP-specific MAD.
• Activated dSMAD2 promotes growth in wing discs, but DAW signaling with MAD or dSMAD2 inhibits growth.
• daw mutants exhibit larval lethality and anal pad defects, with rescue via neuroendocrine cells.

Conclusions:

• dACT and DAW exhibit distinct signaling outcomes through BABO, indicating ligand-specific modulation.
• The phosphorylation of MAD by BABO suggests cross-talk between SMAD pathways.
• Activin-type ligands are likely endocrine signals, and co-receptors may fine-tune BABO signaling.
• This study reveals complex regulation of growth factor signaling in Drosophila development.