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首页> 外文期刊>PLoS Genetics >A Hox complex activates and potentiates the Epidermal Growth Factor signaling pathway to specify Drosophila oenocytes
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A Hox complex activates and potentiates the Epidermal Growth Factor signaling pathway to specify Drosophila oenocytes

机译：Hox复合物激活并增强表皮生长因子信号转导通路，以指定果蝇的成年细胞

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摘要

Hox transcription factors specify distinct cell types along the anterior-posterior axis of metazoans by regulating target genes that modulate signaling pathways. A well-established example is the induction of Epidermal Growth Factor (EGF) signaling by an Abdominal-A (Abd-A) Hox complex during the specification of Drosophila hepatocyte-like cells (oenocytes). Previous studies revealed that Abd-A is non-cell autonomously required to promote oenocyte fate by directly activating a gene (rhomboid) that triggers EGF secretion from sensory organ precursor (SOP) cells. Neighboring cells that receive the EGF signal initiate a largely unknown pathway to promote oenocyte fate. Here, we show that Abd-A also plays a cell autonomous role in inducing oenocyte fate by activating the expression of the Pointed-P1 (PntP1) ETS transcription factor downstream of EGF signaling. Genetic studies demonstrate that both PntP1 and PntP2 are required for oenocyte specification. Moreover, we found that PntP1 contains a conserved enhancer (PntP1OE) that is activated in oenocyte precursor cells by EGF signaling via direct regulation by the Pnt transcription factors as well as a transcription factor complex consisting of Abd-A, Extradenticle, and Homothorax. Our findings demonstrate that the same Abd-A Hox complex required for sending the EGF signal from SOP cells, enhances the competency of receiving cells to select oenocyte cell fate by up-regulating PntP1. Since PntP1 is a downstream effector of EGF signaling, these findings provide insight into how a Hox factor can both trigger and potentiate the EGF signal to promote an essential cell fate along the body plan.
机译：Hox转录因子通过调节调节信号通路的靶基因，沿着后生动物的前后轴指定不同的细胞类型。一个公认的例子是在果蝇肝细胞样细胞（卵母细胞）形成过程中，通过腹部A（Abd-A）Hox复合物诱导表皮生长因子（EGF）信号传导。先前的研究显示，通过直接激活触发感觉器官前体（SOP）细胞EGF分泌的基因（菱形），Abd-A是非必需细胞来自主地促进嗅觉细胞的命运。接收EGF信号的邻近细胞启动了一个很大程度上未知的途径来促进细胞的命运。在这里，我们显示Abd-A在激活EGF信号下游的Pointed-P1（PntP1）ETS转录因子的表达中，在诱导食道细胞命运中也发挥了细胞自治作用。遗传学研究表明，PntP1和PntP2都是制定卵母细胞规格所必需的。此外，我们发现PntP1包含一个保守的增强子（PntP1OE），该蛋白通过直接由Pnt转录因子以及由Abd-A，Extradenticle和Homothorax组成的转录因子复合物的EGF信号在EGF信号中被激活。我们的研究结果表明，从SOP细胞发送EGF信号所需的相同Abd-A Hox复合物通过上调PntP1增强了接收细胞选择食管细胞命运的能力。由于PntP1是EGF信号的下游效应物，因此这些发现为Hox因子如何触发和增强EGF信号以促进沿着人体计划的重要细胞命运提供了见识。

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