Dual origin of the renal tubules in Drosophila:: Mesodermal cells integrate and polarize to establish secretory function
Dual origin of the renal tubules in Drosophila:: Mesodermal cells integrate and polarize to establish secretory function
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DOI：
10.1016/s0960-9822(03)00375-0
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发表时间：
2003-06-17
期刊：
影响因子：
9.2
通讯作者：
Skaer, H
中科院分区：
文献类型：
--
作者：
Denholm, B;Sudarsan, V;Skaer, H
器官由不同来源的细胞组成，它们的发育和分化必须整合起来才能产生生理上连贯的结构。例如，在肾脏发育过程中，上皮中肾管与周围后肾间质之间的一系列相互作用导致肾小管的形成[1]。后肾间充质细胞首先诱导中肾管分支形成输尿管芽[2]，然后它们对从中产生的信号做出反应。结果，间充质细胞被募集到芽，在那里它们在凝结形成肾单位时经历间充质到上皮的转变[3]。相比之下，无脊椎动物的简单肾小管，例如昆虫马尔皮基小管 (MpT)，一直被认为起源于单一组织原基，即通过细胞分裂和增大而生长的上皮芽，并从中分化出一系列专门的亚型 [4-6]。在这里，我们通过证明 MpT 也源自两个细胞群：外胚层上皮芽和周围的间充质中胚层，揭示了果蝇 MpT 发育和脊椎动物肾发生之间意想不到的相似之处。间充质细胞被招募到生长的肾小管中，在那里它们整合并随后分化为生理上独特的肾小管细胞子集（星状细胞），从而经历间充质到上皮的转变。引人注目的是，星状细胞的正常掺入和成熟肾小管的后期生理活性取决于 hibris（哺乳动物 NEPHRIN 的直系同源物）的活性。
Organs are made up of cells from separate origins, whose development and differentiation must be integrated to produce a physiologically coherent structure. For example, during the development of the kidney, a series of interactions between the epithelial mesonephric duct and the surrounding metanephric mesenchyme leads to the formation of renal tubules [1]. Cells of the metanephric mesenchyme first induce branching of the mesonephric duct to form the ureteric buds [2], and they then respond to signals derived from them. As a result, mesenchymal cells are recruited to the buds, where they undergo a mesenchymal-to-epithelial transition as they condense to form nephrons [3]. In contrast, the simple renal tubules of invertebrates, such as insect Malpighian tubules (MpTs), have always been thought to arise from single tissue primordia, epithelial buds that grow by cell division and enlargement and from which a range of specialized subtypes differentiate [4-6]. Here, we reveal unexpected parallels between the development of Drosophila MpTs and vertebrate nephrogenesis by showing that the MpTs also derive from two cell populations: ectodermal epithelial buds and the surrounding mesenchymal mesoderm. The mesenchymal cells are recruited to the growing tubules, where they undergo a mesenchymal-to-epithelial transition as they integrate and subsequently differentiate as a physiologically distinctive subset of tubule cells, the stellate cells. Strikingly, the normal incorporation of stellate cells and the later physiological activity of the mature tubules depend on the activity of hibris, an ortholog of mammalian NEPHRIN.