Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluis Companys, 23, 08011 Barcelona, Spain.
Nat Commun. 2017 Jan 3;8:13815. doi: 10.1038/ncomms13815.
A stable pool of morphogen-producing cells is critical for the development of any organ or tissue. Here we present evidence that JAK/STAT signalling in the Drosophila wing promotes the cycling and survival of Hedgehog-producing cells, thereby allowing the stable localization of the nearby BMP/Dpp-organizing centre in the developing wing appendage. We identify the inhibitor of apoptosis dIAP1 and Cyclin A as two critical genes regulated by JAK/STAT and contributing to the growth of the Hedgehog-expressing cell population. We also unravel an early role of JAK/STAT in guaranteeing Wingless-mediated appendage specification, and a later one in restricting the Dpp-organizing activity to the appendage itself. These results unveil a fundamental role of the conserved JAK/STAT pathway in limb specification and growth by regulating morphogen production and signalling, and a function of pro-survival cues and mitogenic signals in the regulation of the pool of morphogen-producing cells in a developing organ.
稳定的形态发生素产生细胞池对于任何器官或组织的发育都是至关重要的。在这里，我们提供的证据表明，果蝇翅膀中的 JAK/STAT 信号促进 Hedgehog 产生细胞的循环和存活，从而使附近的 BMP/Dpp 组织中心在发育中的翅膀附肢中稳定定位。我们确定凋亡抑制剂 dIAP1 和细胞周期蛋白 A 是受 JAK/STAT 调节的两个关键基因，并有助于 Hedgehog 表达细胞群体的生长。我们还揭示了 JAK/STAT 在保证 Wingless 介导的附肢特化中的早期作用，以及在将 Dpp 组织活性限制在附肢本身中的后期作用。这些结果揭示了保守的 JAK/STAT 途径在通过调节形态发生素的产生和信号传导来调节肢体特化和生长方面的基本作用，以及存活信号和有丝分裂信号在调节发育中的器官中形态发生素产生细胞池方面的功能。
