Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Development. 2010 Mar;137(6):913-22. doi: 10.1242/dev.043224. Epub 2010 Feb 11.
Gas2-like proteins harbour putative binding sites for both the actin and the microtubule cytoskeleton and could thus mediate crosstalk between these cytoskeletal systems. Family members are highly conserved in all metazoans but their in vivo role is not clear. The sole Drosophila Gas2-like gene, CG3973 (pigs), was recently identified as a transcriptional target of Notch signalling and might therefore link cell fate decisions through Notch activation directly to morphogenetic changes. We have generated a null mutant in CG3973 (pigs): pigs(1) mutants are semi-viable but adult flies are flightless, showing indirect flight muscle degeneration, and females are sterile, showing disrupted oogenesis and severe defects in follicle cell differentiation, similar to phenotypes seen when levels of Notch/Delta signalling are perturbed in these tissues. Loss of Pigs leads to an increase in Notch signalling activity in several tissues. These results indicate that Gas2-like proteins are essential for development and suggest that Pigs acts downstream of Notch as a morphogenetic read-out, and also as part of a regulatory feedback loop to relay back information about the morphogenetic state of cells to restrict Notch activation to appropriate levels in certain target tissues.
Gas2 样蛋白具有与肌动蛋白和微管细胞骨架结合的假定结合位点，因此可以介导这两个细胞骨架系统之间的串扰。该家族成员在所有后生动物中高度保守，但它们的体内作用尚不清楚。唯一的果蝇 Gas2 样基因 CG3973（猪）最近被鉴定为 Notch 信号的转录靶标，因此可能通过 Notch 激活将细胞命运决定直接与形态发生变化联系起来。我们已经在 CG3973（猪）中产生了一个 null 突变体：pigs(1) 突变体是半致死的，但成年苍蝇不能飞行，表现出间接飞行肌退化，雌性不育，表现出卵母细胞发生和滤泡细胞分化的严重缺陷，类似于 Notch/Delta 信号水平在这些组织中受到干扰时出现的表型。Pigs 的缺失会导致几种组织中 Notch 信号活性的增加。这些结果表明 Gas2 样蛋白对于发育是必不可少的，并表明 Pigs 作为形态发生的读出器，以及作为将有关细胞形态发生状态的信息反馈回以限制 Notch 激活到某些靶组织中适当水平的调节反馈回路的一部分，在 Notch 下游发挥作用。
