Centro de Biología Molecular Severo Ochoa, CSIC and Universidad Autónoma de Madrid, Madrid 28049, Spain.
Dev Biol. 2013 May 1;377(1):138-53. doi: 10.1016/j.ydbio.2013.02.004. Epub 2013 Feb 26.
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.
果蝇翅膀盘的发育需要 BMP 和 TGFβ 信号通路的活动。BMP 信号对于盘的正确生长和模式形成至关重要，而相关的 TGFβ 途径主要用于生长。BMP 和 TGFβ 途径共享一个共同的共受体（Punt）和一个核效应物（Medea），因此这些途径在正常发育过程中可能相互干扰。在这项工作中，我们专注于 TGFβ 信号在翅膀盘发育过程中的空间激活域和要求。我们发现，Smad2 的磷酸化，即 TGFβ 信号的特定传感器，在翅膀盘中以普遍的方式发生。似乎在翅膀盘中表达四个候选 TGFβ 配体（Activinβ、Dawdle、Maverick 和 Myoglianin）是获得该组织中正常 TGFβ 信号所必需的。我们表明，Baboons，TGFβ 途径的特异性受体，在体内可以磷酸化 Mad，即 BMP 途径的特异性传感器。然而，这种激活仅在翅膀盘当受体在 Smad2 表达降低的背景下组成型激活时发生。在 Smad2 存在的情况下，这是翅膀盘发育的正常情况，高水平的激活的 Baboons 导致 Mad 磷酸化耗尽和 BMP 功能丧失表型。尽管 babo 或 Smad2 表达的缺失以相似的方式减少翅膀刀片的生长，但 Smad2 的缺失也可能导致与异位 BMP 信号相关的表型，这表明该传感器在 Mad 空间激活的调节中具有生理作用。
