Characterisation of the role and regulation of Ultrabithorax in sculpting fine-scale leg morphology

Characterisation of the role and regulation of Ultrabithorax in sculpting fine-scale leg morphology
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Ultrabithorax 在雕刻精细腿部形态中的作用和调节的表征

DOI:
10.1101/2020.06.17.152918
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发表时间:
2020
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通讯作者:
Buffry A
Buffry A
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Buffry A

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Hox基因在胚胎发生过程中表达,并决定动物身体沿着前后轴的区域身份。然而,它们也在胚胎后期起作用,以塑造精细尺度的形态。为了更好地了解Hox基因如何整合到胚后基因调控网络中,我们进一步分析了超双胸(Ubx)在黑腹果蝇腿部发育过程中的作用和调节。Ubx调节第二(T2)和第三(T3)腿对股骨上刚毛和毛状体图案的几个方面。我们发现Ubx对T2股骨近端后部区域毛状体的抑制可能是通过激活microRNA-92 a和microRNA-92 bby这种Hox蛋白的表达来介导的。此外,我们确定了一种新的增强子ofUbx,概括了该基因在T2和T3腿的时间和区域活动。然后,我们使用转录因子(TF)结合基序分析在T2腿细胞中的染色质可及区域,以预测和功能测试可能调节Ubxleg增强子的TF。我们还测试了Ubx辅助因子同胸(Hth)和外齿(Exd)在T2和T3股骨中的作用。我们发现了几种TF,它们可能在上游或与Ubx协同作用,以调节毛状体沿发育股骨的近端-远端轴沿着的图案化,并且毛状体的抑制也需要Hth和Exd。总之,我们的研究结果提供了深入了解Ubxis如何整合到胚胎后基因调控网络,以确定精细尺度的腿形态。
Hox genes are expressed during embryogenesis and determine the regional identity of animal bodies along the antero-posterior axis. However, they also function post-embryonically to sculpt fine-scale morphology. To better understand how Hox genes are integrated into post-embryonic gene regulatory networks, we further analysed the role and regulation ofUltrabithorax(Ubx) during leg development inDrosophila melanogaster.Ubxregulates several aspects of bristle and trichome patterning on the femurs of the second (T2) and third (T3) leg pairs. We found that repression of trichomes in the proximal posterior region of the T2 femur by Ubx is likely mediated by activation of the expression ofmicroRNA-92aandmicroRNA-92bby this Hox protein. Furthermore, we identified a novel enhancer ofUbxthat recapitulates the temporal and regional activity of this gene in T2 and T3 legs. We then used transcription factor (TF) binding motif analysis in regions of accessible chromatin in T2 leg cells to predict and functionally test TFs that may regulate theUbxleg enhancer. We also tested the role of the Ubx co-factors Homothorax (Hth) and Extradenticle (Exd) in T2 and T3 femurs. We found several TFs that may act upstream or in concert with Ubx to modulate trichome patterning along the proximo-distal axis of developing femurs and that the repression of trichomes also requires Hth and Exd. Taken together our results provide insights into howUbxis integrated into a post-embryonic gene regulatory network to determine fine-scale leg morphology.
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