Vishal Kumar, Brooks David S, Bawa Simranjot, Gameros Samantha, Stetsiv Marta, Geisbrecht Erika R
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66506.
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66506
Genetics. 2017 May;206(1):199-213. doi: 10.1534/genetics.116.193813. Epub 2017 Mar 1.
Adult muscle precursor (AMP) cells located in the notum of the larval wing disc undergo rapid amplification and eventual fusion to generate the indirect flight muscles (IFMs). Here we find that loss of Moleskin (Msk) function in these wing disc-associated myoblasts reduces the overall AMP pool size, resulting in the absence of IFM formation. This myoblast loss is due to a decrease in the AMP proliferative capacity and is independent of cell death. In contrast, disruption of Msk during pupal myoblast proliferation does not alter the AMP number, suggesting that Msk is specifically required for larval AMP proliferation. It has been previously shown that Wingless (Wg) signaling maintains expression of the Vestigial (Vg) transcription factor in proliferating myoblasts. However, other factors that influence Wg-mediated myoblast proliferation are largely unknown. Here we examine the interactions between Msk and the Wg pathway in regulation of the AMP pool size. We find that a myoblast-specific reduction of Msk results in the absence of Vg expression and a complete loss of the Wg pathway readout β-catenin/Armadillo (Arm). Moreover, knockdown abolishes expression of the Wg target Ladybird (Lbe) in leg disc myoblasts. Collectively, our results provide strong evidence that Msk acts through the Wg signaling pathway to control myoblast pool size and muscle formation by regulating Arm stability or nuclear transport.
位于幼虫翅盘背板的成年肌肉前体细胞(AMP)会经历快速增殖并最终融合,以生成间接飞行肌(IFM)。在此,我们发现这些与翅盘相关的成肌细胞中,Moleskin(Msk)功能缺失会减小AMP的总体数量,导致无法形成IFM。这种成肌细胞的缺失是由于AMP增殖能力下降,且与细胞死亡无关。相比之下,在蛹期成肌细胞增殖过程中破坏Msk不会改变AMP数量,这表明Msk是幼虫AMP增殖所特需的。先前研究表明,无翅(Wg)信号通路可维持增殖成肌细胞中残翅(Vg)转录因子的表达。然而,影响Wg介导的成肌细胞增殖的其他因素在很大程度上尚不清楚。在此,我们研究了Msk与Wg信号通路在调节AMP数量方面的相互作用。我们发现,成肌细胞特异性降低Msk会导致Vg表达缺失,以及Wg信号通路的读数β-连环蛋白/犰狳(Arm)完全丧失。此外,敲低会消除腿部盘状成肌细胞中Wg靶标瓢虫(Lbe)的表达。总的来说,我们的结果提供了强有力的证据,表明Msk通过Wg信号通路发挥作用,通过调节Arm的稳定性或核转运来控制成肌细胞数量和肌肉形成。