Six1 and Six4 are essential for Gdnf expression in the metanephric mesenchyme and ureteric bud formation, while Six1 deficiency alone causes mesonephric-tubule defects
Six1 and Six4 are essential for Gdnf expression in the metanephric mesenchyme and ureteric bud formation, while Six1 deficiency alone causes mesonephric-tubule defects
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DOI：
10.1016/j.mod.2007.01.002
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发表时间：
2007-04-01
影响因子：
2.6
通讯作者：
Nishinakamura, Ryuichi
中科院分区：
文献类型：
--
作者：
Kobayashi, Hiroki;Kawakami, Kiyoshi;Nishinakamura, Ryuichi
输尿管芽上皮和后肾间质之间的相互作用对于肾脏发育很重要。 Six1和Six4是果蝇正眼果蝇的哺乳动物同源物，它们在肾源性间充质中共表达。 Six1 缺陷小鼠表现出不同的肾脏缺陷，而 Six4 缺陷小鼠则没有明显的异常。在这里，我们报告了我们制备的 Six1/Six4 缺陷小鼠，以阐明 Six4 在 Six1 缺陷肾脏发育中的功能。 Six1/Six4缺陷小鼠比Six1缺陷小鼠表现出更严重的肾脏表型；所有检查的新生儿均观察到肾脏和输尿管发育不全。 Six1/Six4缺陷的后肾间充质细胞定向为肾谱系，但未能表达Pax2、Pax8或Gdnf，而在Six1缺陷的情况下，这些基因的表达部分减少或不变。因此，Six4在后肾间充质中与Six1协同调节Gdnf表达水平；这可以解释 Six1/ Six4 缺陷小鼠中输尿管芽的缺失。相比之下，单独的 Six1 缺陷会导致中肾小管形成缺陷，并且这些缺陷在 Six1/Six4 缺陷的中肾中并未加剧。这些结果强调了一个事实，即 Six1 和 Six4 在后肾中具有协同功能，但在中肾中则不然。 (c) 2007 Elsevier Ltd. 保留所有权利。
Interaction between the ureteric-bud epithelium and the metanephric mesenchyme is important for kidney development. Six1 and Six4 are the mammalian homologs of Drosophila sine oculis, and they are coexpressed in the nephrogenic mesenchyme. Six1-deficient mice show varying kidney defects, while Six4-deficient mice have no apparent abnormalities. Here, we report Six1/Six4-deficient mice that we generated in order to elucidate the functions of Six4 in Six1-deficient kidney development. The Six1/Six4-deficient mice exhibited more severe kidney phenotypes than the Six1-deficient mice; kidney and ureter agenesis was observed in all the neonates examined. The Six1/Six4-deficient metanephric mesenchyme cells were directed toward kidney lineage but failed to express Pax2, Pax8, or Gdnf, whereas the expression of these genes was partially reduced or unchanged in the case of Six1 deficiency. Thus, Six4 cooperates with Six1 in the metanephric mesenchyme to regulate the level of Gdnf expression; this could explain the absence of the ureteric bud in the Six1/ Six4-deficient mice. In contrast, Six1 deficiency alone caused defects in mesonephric-tubule formation, and these defects were not exacerbated in the Six1/Six4-deficient mesonephros. These results highlight the fact that Six1 and Six4 have collaborative functions in the metanephros but not in the mesonephros. (c) 2007 Elsevier Ltd. All rights reserved.