An Enhancer of the Drosophila Ubx Hox Gene is Essential for Segment-Specific Sense Organ Patterning
Creators: name: Balyan, Arjun
Publisher: name: University of Illinois at Chicago
Year: 2023
Subjects: Uncategorized

description: The molecular mechanisms underlying generation of morphological diversity among homologous animal structures have been extensively studied. The legs of Drosophila melanogaster are a great example of homologous structures. The adult has three pairs of legs, one on each thoracic segment, and each pair exhibits distinct morphology based on its segment of origin. The legs are covered by an array of sense organs that are components of the peripheral nervous system (PNS). The pathways that establish the patterning of mechanosensory bristles, both large macrochaetae (MC) and smaller microchaetae (mC) have been extensively investigated in the legs and notum. The global regulators of leg development, Decapentaplegic (Dpp), Hedgehog (Hh), and Wingless (Wg), establish longitudinal bristle rows (LBRs) in all three pairs of legs. Previous studies in our lab have shown that modulated Hox gene expression of Sex combs reduced (Scr) and Ultrabithorax (Ubx) in the T1 and the T3 legs, respectively, alters the LBR pathway to give rise to transverse bristle rows (TBRs) instead of the LBRs. This suggests that both Scr and Ubx are targets of the leg intrasegmental patterning pathways and function downstream of these pathways to generate morphological diversity among the legs. To determine the mechanisms by which Hox genes function to generate segment-specific sense organ patterns in the limb primordia, it is important to understand how the modulated Hox gene expression is established. Therefore, we sought to uncover genetic and molecular mechanisms by which modulated expression of the Hox gene Ubx is regulated in later stages of development, such as the imaginal disc and the pupal stages. In this study, we have investigated the modulated expression of Ubx in precise domains of the third thoracic (T3) leg which correlates with the TBR primordia, and the focus has been on regulation of Ubx by genes that pattern legs along the proximal-distal (P/D) axis, such as Distalless (Dll), dachshund (dac), and Bric-a-brac (bab). The expression analysis reveals that Ubx expression is elevated in the medial domain of the leg where TF’s Dll and Dac are co-expressed. Through our genetic studies, we have found that Dll activates the expression of elevated Ubx expression, which is observed in the distal-most cells of tibia, tarsal segments (ta) 1 and 2 of the T3 legs. bab regulates the differential Ubx expression by repressing its expression in distal leg ta3-5 segments. We have also identified an enhancer element that controls elevated Ubx expression in the T3 leg-specific TBR sense organ primordia. We show, through our functional analysis of the enhancer element and have identified multiple consensus Dll-sites that are necessary for enhancer activity. Moreover, we have determined that the enhancer is essential for elevated Ubx expression and development of proper TBR sense organ patterns in T3 legs. Our work provides a new perspective on function and regulation of modulated Hox gene expression in limb fields and implicates localized modulated Hox gene expression as a key mechanism through which Hox genes fine-tune morphological features of limbs.