DISTAL-LESS REGULATION DURING DROSOPHILA LEG DEVELOPMENT

这项工作的主要目标是了解分子机制 这是整合信号通路的基础， 附肢的远端（PD）生长和图案化。 尽管宽 节肢动物和脊椎动物体的多样性和进化历史 细胞壁生长，参与细胞壁生长的信号通路， 图案是保守的。 然而， 这些途径用于介导形态发生是未知的。 因为 这些途径的复杂性和相互联系， 明确阐明其功能是为了直接， 效应分子与靶基因的功能性相互作用。 的 该提案中概述的实验旨在从基因上识别 并在分子水平上表征控制 果蝇足盘中Distal-less基因的表达， 并以生物化学的方法确定它们所依赖的反式作用因子， 回答。 无远端似乎是基因组中的一个关键成员， 控制肢体发育的程序，以及识别 调节其表达的成分将提供一个关键的分子 胚轴提供的位置信息与 形成PD轴。 这项工作还将提供机械 探索附属物形成是否通过 在不同的动物中也有类似的过程。

The broad goal of this work is to understand the molecular mechanisms that underlie the integration of signaling pathways to effect proximal- distal (PD) growth and patterning of appendages. Despite the wide diversity and evolutionary history of arthropod and vertebrate body wall outgrowths, the signaling pathways that are involved in their patterning are conserved. However, the molecular mechanisms by which these pathways act to mediate morphogenesis are unknown. Because of the complexity and interconnectivity of these pathways, the way to unambiguously elucidate their functions is to demonstrate direct, functional interaction of effector molecules with target genes. The experiments outlined in this proposal are designed to identify genetically and characterize molecularly cis-regulatory elements that control expression of the Distal-less gene in the Drosophila leg imaginal disc, and to biochemically identify the trans-acting factors to which they respond. Distal-less appears to be a key member of the genetic program that controls limb development, and identification of the components that regulate its expression will provide a crucial molecular link between positional information provided by embryonic axes and formation of the PD axis. This work will also provide the mechanistic foundation for exploring whether appendage formation operates by similar processes in different animals.