Hevia Covadonga F, López-Varea Ana, Esteban Nuria, de Celis Jose F
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Scientíficas and Universidad Autónoma de Madrid, 28049, Spain.
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Scientíficas and Universidad Autónoma de Madrid, 28049, Spain
Genetics. 2017 May;206(1):231-249. doi: 10.1534/genetics.116.197228. Epub 2017 Mar 17.
Transforming Growth Factor β (TGFβ) 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 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 TGFβ signaling promotes cell division in imaginal discs, or what the interactions between TGFβ activity and other signaling pathways regulating cell proliferation are. In this work, we have explored the disc autonomous function of TGFβ that promotes wing imaginal disc growth. We have studied the genetic interactions between TGFβ 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 TGFβ 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 TGFβ could affect cell proliferation by regulating the metabolic fitness of imaginal cells.
转化生长因子β(TGFβ)信号传导对细胞增殖具有复杂的影响,它在分化细胞中起到阻止细胞分裂的作用,但同时也促进未成熟细胞的分裂。该信号通路的活性主要是刺激神经和上皮组织的增殖所必需的。最有趣的是,这种功能并非细胞分裂绝对必需的,但对于这些组织达到其正确大小却是必需的。目前尚不清楚TGFβ信号传导如何促进成虫盘的细胞分裂,也不清楚TGFβ活性与其他调节细胞增殖的信号通路之间的相互作用是什么。在这项工作中,我们探索了TGFβ促进翅成虫盘生长的盘自主功能。我们研究了TGFβ信号传导与其他调节翅盘生长的信号通路之间的遗传相互作用,如胰岛素和Hippo/Salvador/Warts信号通路,以及细胞周期调节因子。我们还利用表达谱鉴定了一系列影响成虫生长的TGFβ候选靶基因。这些候选基因对应于参与多种生化过程调节的基因,包括细胞代谢的不同方面,这表明TGFβ可能通过调节成虫细胞的代谢适应性来影响细胞增殖。