Bejarano Fernando, Luque Carlos M, Herranz Héctor, Sorrosal Georgina, Rafel Neus, Pham Thu Thuy, Milán Marco
Institució Catalana de Recerca i Estudis Avançats and Institute for Research in Biomedicine, 08028 Barcelona, Spain.
Genetics. 2008 Jan;178(1):307-23. doi: 10.1534/genetics.107.081869.
The Drosophila wing primordium is subdivided into a dorsal (D) and a ventral (V) compartment by the activity of the LIM-homeodomain protein Apterous in D cells. Cell interactions between D and V cells induce the activation of Notch at the DV boundary. Notch is required for the maintenance of the compartment boundary and the growth of the wing primordium. Beadex, a gain-of-function allele of dLMO, results in increased levels of dLMO protein, which interferes with the activity of Apterous and results in defects in DV axis formation. We performed a gain-of-function enhancer-promoter (EP) screen to search for suppressors of Beadex when overexpressed in D cells. We identified 53 lines corresponding to 35 genes. Loci encoding for micro-RNAs and proteins involved in chromatin organization, transcriptional control, and vesicle trafficking were characterized in the context of dLMO activity and DV boundary formation. Our results indicate that a gain-of-function genetic screen in a sensitized background, as opposed to classical loss-of-function-based screenings, is a very efficient way to identify redundant genes involved in a developmental process.
果蝇翅原基通过D细胞中LIM同源域蛋白Apterous的活性被细分为背侧(D)和腹侧(V)区室。D细胞和V细胞之间的细胞相互作用诱导了DV边界处Notch的激活。Notch对于维持区室边界和翅原基的生长是必需的。Beadex是dLMO的一个功能获得性等位基因,导致dLMO蛋白水平升高,这会干扰Apterous的活性并导致DV轴形成缺陷。我们进行了一项功能获得性增强子-启动子(EP)筛选,以寻找在D细胞中过表达时Beadex的抑制因子。我们鉴定出了对应于35个基因的53个品系。在dLMO活性和DV边界形成的背景下,对编码微小RNA和参与染色质组织、转录控制及囊泡运输的蛋白质的基因座进行了表征。我们的结果表明,与基于经典功能丧失的筛选相反,在敏感背景下进行功能获得性遗传筛选是鉴定参与发育过程的冗余基因的一种非常有效的方法。