Activation and function of TGFβ signalling during Drosophila wing development and its interactions with the BMP pathway

Abstract

The development of the Drosophila wing disc requires the activities of the BMP and TGFβ signalling pathways. BMP signalling is critical for the correct growth and patterning of the disc, whereas the related TGFβ pathway is mostly required for growth. The BMP and TGFβ pathways share a common co-receptor (Punt) and a nuclear effector (Medea), and consequently it is likely that these pathways can interfere with each other during normal development. In this work we focus on the spatial activation domains and requirements for TGFβ signalling during wing disc development. We found that the phosphorylation of Smad2, the specific transducer for TGFβ signalling, occurs in a generalised manner in the wing disc. It appears that the expression of the four candidate TGFβ ligands (Activinβ, Dawdle, Maverick and Myoglianin) in the wing disc is required to obtain normal levels of TGFβ signalling in this tissue. We show that Baboon, the specific receptor of the TGFβ pathway, can phosphorylate Mad, the specific transducer of the BMP pathway, in vivo. However, this activation only occurs in the wing disc when the receptor is constitutively activated in a background of reduced expression of Smad2. In the presence of Smad2, the normal situation during wing disc development, high levels of activated Baboon lead to a depletion in Mad phosphorylation and to BMP loss-of-function phenotypes. Although loss of either babo or Smad2 expression reduce growth in the wing blade in a similar manner, loss of Smad2 can also cause phenotypes related to ectopic BMP signalling, suggesting a physiological role for this transducer in the regulation of Mad spatial activation.

A Search for Genes Mediating the Growth-Promoting Function of TGFβ in the Drosophila melanogaster Wing Disc

“…The size defects observed upon loss of Smad2 are not caused by gross defects in cell growth or viability, or by defects in any particular cell cycle transition, but they can be mostly attributed to a decrease in cell proliferation rates (Hevia and de Celis 2013). We examined the proliferation of Smad F4 mutant cells by clonal analysis in Smad2 F4 FRT19A/ FRT19A Ubi-GFP hs-FLP1.22 wing discs and found that Smad2 homozygous mutant clones are smaller than their wild-type twins (Figure 1,M and N).…”

“…We have previously shown that changes in the function of Smad2 do not cause specific defects in either the G1 to S or G2 to M cell cycle transitions (Hevia and de Celis 2013), suggesting that both steps might be affected to a similar extent. We examined the expression of two cell cycle regulators, CycE and string, in loss-of-function Smad2 wing discs.…”

“…On the other hand, TGFb signaling acting in epithelial cells is also required for the wing disc to reach its normal size (Brummel et al 1999;Hevia and de Celis 2013). In this manner, the ring gland and the wing epithelium are places of ligand production and accumulate phosphorylated Smad2 (Brummel et al 1999;Hevia and de Celis 2013).…”

TGF-β signaling in insects regulates metamorphosis via juvenile hormone biosynthesis

“…To identify ligands that may be redundant for Gb'dpp, RNAi was used to target various Gryllus homologs of the Drosophila TGF-β family members (21), including Gb'gbb, activinß (Gb'actβ), maverick (Gb'mav), and myoglianin (Gb'myo).…”

A decision underlies phototaxis in an insect

“…We wondered whether this simultaneous low phototaxis and the absence of wing-clipping effect was due to a specific effect of these mutations or a general consequence of both manipulations altering the flies' wing utility. To tackle this question, we tested three lines with flight impairments, the flightless PKC d mutant, the wings of which are indistinguishable from wild-type wings (figure 2d), the CyO balancer line with curly wings, and a transgenic line in which the wings were deformed due to an overexpression of a constitutively active form of the baboon receptor in wing imaginal discs (A9.babo QD [36]). …”