A Distalless-responsive enhancer of the Hox gene Sex combs reduced is required for segment- and sex-specific sensory organ development in Drosophila

Hox genes are involved in the patterning of animal body parts at multiple levels of regulatory hierarchies. Early expression of Hox genes in different domains along the embryonic anterior-posterior (A/P) axis in insects, vertebrates, and other animals establishes segmental or regional identity. However, Hox gene function is also required later in development for the patterning and morphogenesis of limbs and other organs. In Drosophila, spatiotemporal modulation of Sex combs reduced (Scr) expression within the first thoracic (T1) leg underlies the generation of segment- and sex-specific sense organ patterns. High Scr expression in defined domains of the T1 leg is required for the development of T1-specific transverse bristle rows in both sexes and sex combs in males, implying that the patterning of segment-specific sense organs involves incorporation of Scr into the leg development and sex determination gene networks. We sought to gain insight into this process by identifying the cis-and trans-regulatory factors that direct Scr expression during leg development. We have identified two cis-regulatory elements that control spatially modulated Scr expression within T1 legs. One of these enhancers directs sexually dimorphic expression and is required for the formation of T1-specific bristle patterns. We show that the Distalless and Engrailed homeodomain transcription factors act through sequences in this enhancer to establish elevated Scr expression in spatially defined domains. This enhancer functions to integrate Scr into the intrasegmental gene regulatory network, such that Scr serves as a link between leg patterning, sex determination, and sensory organ development.

Hox基因在动物体部结构的分级调控体系中扮演着重要角色。在昆虫、脊椎动物及其他动物胚胎前后的（A/P）轴的不同领域中，Hox基因的早期表达确立了节段或区域的身份。然而，Hox基因的功能在发育的后期对于肢体和其他器官的图案化与形态发生亦不可或缺。在果蝇中，性梳减少（Scr）基因在第一胸节（T1）腿中的时空调节是生成节段和性别特异性感觉器官模式的基础。在T1腿的特定领域中，高Scr表达对于两性T1特异的横纹毛排和雄性的性梳发育是必需的，这表明节段特异性感觉器官的图案化涉及将Scr整合入腿部发育与性别决定基因网络。我们旨在通过识别指导Scr在腿部发育期间表达的顺式和反式调控因子来深入了解此过程。我们已确定两个控制T1腿中Scr空间调节表达的顺式调控元件。其中之一作为增强子，指导性二形性表达，并对于形成T1特异的毛排模式是必需的。我们证实远端发育不全（Distalless）和 engrailed（Engrailed）同源域转录因子通过此增强子中的序列实现，以在空间定义的领域中提升Scr表达。此增强子功能在于将Scr整合入节段内基因调控网络，使得Scr成为腿部图案化、性别决定与感觉器官发育之间的联系。