Injury-induced BMP signaling negatively regulates Drosophila midgut homeostasis.
Injury-induced BMP signaling negatively regulates Drosophila midgut homeostasis.
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DOI：
10.1083/jcb.201302049
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发表时间：
2013-06-10
期刊：
影响因子：
--
通讯作者：
Ohlstein B
中科院分区：
文献类型：
--
作者：
Guo Z;Driver I;Ohlstein B
中肠损伤诱导的BMP信号负调控肠干细胞分裂，而区域组成性BMP信号促进铜细胞分化。虽然对损伤诱导的信号增加黑腹果蝇中肠肠干细胞（ISC）增殖速率的了解很多，但在很大程度上不知道ISC活性如何在损伤后恢复到静止状态。在本文中，我们表明，骨形态发生蛋白（BMP）信号通路在中肠稳态具有双重功能。中肠中部组成型BMP信号通路激活通过促进铜细胞分化介导区域特化。在前中肠和后中肠，损伤诱导的BMP信号传导在ISCs中自主发挥作用，以限制损伤后的增殖和干细胞数量。中肠上皮中BMP信号传导通路成员的缺失或内脏肌中BMP信号传导配体decapentaplegic的缺失导致与幼年型息肉病综合征（一种由BMP信号传导通路组分突变引起的人类肠道肿瘤）相似的表型。我们的数据建立了损伤和增生之间的新联系，并可能为BMP信号突变如何驱动人类肠癌的形成提供见解。
Injury-induced BMP signaling in the midgut negatively regulates intestinal stem cell division, whereas regional constitutive BMP signaling promotes copper cell differentiation. Although much is known about injury-induced signals that increase rates of Drosophila melanogaster midgut intestinal stem cell (ISC) proliferation, it is largely unknown how ISC activity returns to quiescence after injury. In this paper, we show that the bone morphogenetic protein (BMP) signaling pathway has dual functions during midgut homeostasis. Constitutive BMP signaling pathway activation in the middle midgut mediated regional specification by promoting copper cell differentiation. In the anterior and posterior midgut, injury-induced BMP signaling acted autonomously in ISCs to limit proliferation and stem cell number after injury. Loss of BMP signaling pathway members in the midgut epithelium or loss of the BMP signaling ligand decapentaplegic from visceral muscle resulted in phenotypes similar to those described for juvenile polyposis syndrome, a human intestinal tumor caused by mutations in BMP signaling pathway components. Our data establish a new link between injury and hyperplasia and may provide insight into how BMP signaling mutations drive formation of human intestinal cancers.
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