Bieli Dimitri, Kanca Oguz, Requena David, Hamaratoglu Fisun, Gohl Daryl, Schedl Paul, Affolter Markus, Slattery Matthew, Müller Martin, Estella Carlos
Biozentrum, University of Basel, Basel, Switzerland.
Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
PLoS Genet. 2015 Oct 15;11(10):e1005376. doi: 10.1371/journal.pgen.1005376. eCollection 2015 Oct.
The subdivision of cell populations in compartments is a key event during animal development. In Drosophila, the gene apterous (ap) divides the wing imaginal disc in dorsal vs ventral cell lineages and is required for wing formation. ap function as a dorsal selector gene has been extensively studied. However, the regulation of its expression during wing development is poorly understood. In this study, we analyzed ap transcriptional regulation at the endogenous locus and identified three cis-regulatory modules (CRMs) essential for wing development. Only when the three CRMs are combined, robust ap expression is obtained. In addition, we genetically and molecularly analyzed the trans-factors that regulate these CRMs. Our results propose a three-step mechanism for the cell lineage compartment expression of ap that includes initial activation, positive autoregulation and Trithorax-mediated maintenance through separable CRMs.
细胞群体在不同区域的细分是动物发育过程中的关键事件。在果蝇中,无翅基因(ap)将翅成虫盘划分为背侧和腹侧细胞谱系,并且是翅形成所必需的。ap作为背侧选择基因的功能已得到广泛研究。然而,其在翅发育过程中的表达调控却知之甚少。在本研究中,我们分析了内源性位点的ap转录调控,并鉴定出三个对翅发育至关重要的顺式调控模块(CRM)。只有当这三个CRM结合在一起时,才能获得强劲的ap表达。此外,我们对调控这些CRM的反式因子进行了遗传学和分子分析。我们的结果提出了一种ap细胞谱系区域表达的三步机制,包括通过可分离的CRM进行初始激活、正向自调控和三胸复合物介导的维持。