Organista María F, Martín Mercedes, de Celis Jesus M, Barrio Rosa, López-Varea Ana, Esteban Nuria, Casado Mar, de Celis Jose F
Centro de Biología Molecular Severo Ochoa, CSIC and Universidad Autónoma de Madrid, C/Nicolás Cabrera, 1. Universidad Autónoma de Madrid, Madrid, Spain.
PLoS Genet. 2015 Aug 4;11(8):e1005370. doi: 10.1371/journal.pgen.1005370. eCollection 2015 Aug.
The Drosophila genes spalt major (salm) and spalt-related (salr) encode Zn-finger transcription factors regulated by the Decapentaplegic (Dpp) signalling pathway in the wing imaginal disc. The function of these genes is required for cell survival and proliferation in the central region of the wing disc, and also for vein patterning in the lateral regions. The identification of direct Salm and Salr target genes, and the analysis of their functions, are critical steps towards understanding the genetic control of growth and patterning of the Drosophila wing imaginal disc by the Dpp pathway. To identify candidate Salm/Salr target genes, we have compared the expression profile of salm/salr knockdown wing discs with control discs in microarray experiments. We studied by in situ hybridization the expression pattern of the genes whose mRNA levels varied significantly, and uncovered a complex transcription landscape regulated by the Spalt proteins in the wing disc. Interestingly, candidate Salm/Salr targets include genes which expression is turned off and genes which expression is positively regulated by Salm/Salr. Furthermore, loss-of-function phenotypic analysis of these genes indicates, for a fraction of them, a requirement for wing growth and patterning. The identification and analysis of candidate Salm/Salr target genes opens a new avenue to reconstruct the genetic structure of the wing, linking the activity of the Dpp pathway to the development of this epithelial tissue.
果蝇基因“spalt major”(salm)和“spalt-related”(salr)编码锌指转录因子,这些因子在翅成虫盘(wing imaginal disc)中受“Decapentaplegic”(Dpp)信号通路调控。这些基因的功能对于翅盘中央区域的细胞存活和增殖以及外侧区域的翅脉形成都是必需的。鉴定Salm和Salr的直接靶基因并分析其功能,是理解Dpp通路对果蝇翅成虫盘生长和模式形成进行遗传控制的关键步骤。为了鉴定候选的Salm/Salr靶基因,我们在微阵列实验中比较了salm/salr敲低的翅盘与对照翅盘的表达谱。我们通过原位杂交研究了mRNA水平有显著变化的基因的表达模式,揭示了翅盘中由Spalt蛋白调控的复杂转录格局。有趣的是,候选的Salm/Salr靶基因包括表达被关闭的基因以及表达受Salm/Salr正向调控的基因。此外,对这些基因的功能缺失表型分析表明,其中一部分基因对翅的生长和模式形成是必需的。鉴定和分析候选的Salm/Salr靶基因开辟了一条重建翅的遗传结构的新途径,将Dpp通路的活性与这种上皮组织的发育联系起来。