Strategies for exploring TGF-β signaling in Drosophila

Abstract

The TGF-beta pathway is an evolutionarily conserved signal transduction module that mediates diverse biological processes in animals. In Drosophila, both the BMP and Activin branches are required for viability. Studies rooted in classical and molecular genetic approaches continue to uncover new developmental roles for TGF-beta signaling. We present an overview of the secreted ligands, transmembrane receptors and cellular Smad transducer proteins that comprise the core pathway in Drosophila. An assortment of tools have been developed to conduct tissue-specific loss and gain-of-function experiments for these pathway components. We discuss the deployment of these reagents, with an emphasis on appropriate usage and limitations of the available tools. Throughout, we note reagents that are in need of further improvement of development, and signaling features requiring further study. A general theme is that comparison of phenotypes for ligands, receptors, and Smads can be used to map tissue interactions, and to separate canonical and non-canonical signaling activities. Core TGF-beta signaling components are subject to multiple layers of regulation, and are coupled to context-specific inputs and outputs. In addition to fleshing out how TGF-beta signaling serves the fruit fly, we anticipate that future studies will uncover new regulatory nodes and modes and will continue to advance paradigms for how TGF-beta signaling regulates general developmental processes.

CTCF-dependent co-localization of canonical Smad signaling factors at architectural protein binding sites in D. melanogaster

“…43 BMP ligands bind the type I serine-threonine receptors Thickveins (Tkv) and Saxophone (Sax) to induce C-terminal phosphorylation of the R-Smad Mothers against DPP (Mad). 44,45 TGF-b/Activin ligands signal through splice isoforms of the Baboon receptor to activate the R-Smad dSmad2 (Smad on X).…”

TGF-β signaling regulates resistance to parasitic nematode infection in Drosophila melanogaster

“…Molecular and functional analysis of TGF-β signaling core components in model systems has the potential to provide a deep understanding of their activity and exact role in modulating a diverge range of physiological processes as well as controlling different steps of complex interactions within the organism (Li et al, 2006). In the fruit fly D. melanogaster , the Activin and BMP signals are transduced via receptor and Smad phosphorylation events that are essentially identical to those described for vertebrate TGF-β family signaling (Zi et al, 2012; Peterson and O’Connor, 2014). Interestingly, it was previously shown that TGF-β superfamily signals modulate the D. melanogaster immune response to wounding and bacterial infection (Clark et al, 2011).…”

Ret and Substrate-Derived TGF-β Maverick Regulate Space-Filling Dendrite Growth in Drosophila Sensory Neurons

“…TGF-β ligands are evolutionary conserved signaling modules present in all metazoans and the closest conserved homologs of the mammalian GDNF family (Peterson and O’Connor, 2014; Saarma, 2000). So far, only activin has been implicated in the regulation of dendritic organization by restricting dendritic field size of amacrine cells through TGF-β signaling (Ting et al, 2014), whereas Mav can act as a glial-derived cue regulating neuromuscular junction (NMJ) growth (Fuentes-Medel et al, 2012).…”