Cells perceive their microenvironment through chemical and physical cues. However, how the mechanical signals are interpreted during embryonic tissue deformation to result in specific cell behaviors is largely unknown. The Yap/Taz family of transcriptional co-activators has emerged as an important regulator of tissue growth and regeneration, responding to physical cues from the extracellular matrix, and to cell shape and actomyosin cytoskeletal changes. In this study, we demonstrate the role of Yap/Taz-TEAD activity as a sensor of mechanical signals in the regulation of the progenitor behavior of boundary cells during zebrafish hindbrain compartmentalization. Monitoring of in vivo Yap/Taz activity during hindbrain segmentation indicated that boundary cells responded to mechanical cues in a cellautonomous manner through Yap/Taz-TEAD activity. Cell-lineage analysis revealed that Yap/Taz-TEAD boundary cells decreased their proliferative activity when Yap/Taz-TEAD activity ceased, which preceded changes in their cell fate from proliferating progenitors to differentiated neurons. Functional experiments demonstrated the pivotal role of Yap/Taz-TEAD signaling in maintaining progenitor features in the hindbrain boundary cell population.

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.

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Transforming Growth Factor b (TGFb) signaling has a complex influence on cell proliferation, acting to stop cell division in differentiating cells, but also promoting cell division in immature cells. The activity of the pathway in Drosophila is mostly required to stimulate the proliferation of neural and epithelial tissues. Most interestingly, this function is not absolutely required for cell division, but it is needed for these tissues to reach their correct size. It is not known how TGFb signaling promotes cell division in imaginal discs, or what the interactions between TGFb activity and other signaling pathways regulating cell proliferation are. In this work, we have explored the disc autonomous function of TGFb that promotes wing imaginal disc growth. We have studied the genetic interactions between TGFb signaling and other pathways regulating wing disc growth, such as the Insulin and Hippo/Salvador/Warts pathways, as well as cell cycle regulators. We have also identified a collection of TGFb candidate target genes affecting imaginal growth using expression profiles. These candidates correspond to genes participating in the regulation of a variety of biochemical processes, including different aspects of cell metabolism, suggesting that TGFb could affect cell proliferation by regulating the metabolic fitness of imaginal cells.