Hox10 genes function in kidney development in the differentiation and integration of the cortical stroma.
Hox10 genes function in kidney development in the differentiation and integration of the cortical stroma.
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DOI：
10.1371/journal.pone.0023410
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wellik DM
中科院分区：
文献类型：
--
作者：
Yallowitz AR;Hrycaj SM;Short KM;Smyth IM;Wellik DM
器官发生需要不同细胞群的分化和整合以形成功能器官。在肾脏中，输尿管和肾源性间充质之间的相互作用是器官形成所必需的。此外，基质细胞的分化和整合对于该器官的正常发育也是必要的。关于皮质基质细胞的起源以及参与其形成和功能的途径仍有许多问题有待了解。通过在Hox10旁系同源组基因中产生三重突变体，我们证明了Hox10基因在肾脏发育中起着关键作用。仔细检查对照肾脏显示，Foxd 1表达的基质前体细胞首先在后肾间充质前方的帽状图案中观察到，并且这些细胞随后随着发育的进行向后整合到肾脏外周中。虽然表达Foxd1的皮质基质细胞的初始帽状模式在Hox10突变体中不受影响，但这些细胞未能正确整合到肾脏中，并且不分化形成肾包膜。与皮质基质细胞功能丧失一致，Hox10突变肾显示输尿管分支减少和异常，肾发生减少。因此，这些数据提供了关键的新见解的细胞和遗传机制，在肾器官发生皮质细胞发育。这些结果，结合以往的证据表明，Hox 11基因是必要的图案的后肾间充质，支持一个模型，即在生肾索不同的人群由独特的Hox代码进行调节，并表示差异Hox功能沿着AP轴的生肾索是至关重要的分化和整合这些细胞类型在肾脏器官发生。
Organogenesis requires the differentiation and integration of distinct populations of cells to form a functional organ. In the kidney, reciprocal interactions between the ureter and the nephrogenic mesenchyme are required for organ formation. Additionally, the differentiation and integration of stromal cells are also necessary for the proper development of this organ. Much remains to be understood regarding the origin of cortical stromal cells and the pathways involved in their formation and function. By generating triple mutants in the Hox10 paralogous group genes, we demonstrate that Hox10 genes play a critical role in the developing kidney. Careful examination of control kidneys show that Foxd1-expressing stromal precursor cells are first observed in a cap-like pattern anterior to the metanephric mesenchyme and these cells subsequently integrate posteriorly into the kidney periphery as development proceeds. While the initial cap-like pattern of Foxd1-expressing cortical stromal cells is unaffected in Hox10 mutants, these cells fail to become properly integrated into the kidney, and do not differentiate to form the kidney capsule. Consistent with loss of cortical stromal cell function, Hox10 mutant kidneys display reduced and aberrant ureter branching, decreased nephrogenesis. These data therefore provide critical novel insights into the cellular and genetic mechanisms governing cortical cell development during kidney organogenesis. These results, combined with previous evidence demonstrating that Hox11 genes are necessary for patterning the metanephric mesenchyme, support a model whereby distinct populations in the nephrogenic cord are regulated by unique Hox codes, and that differential Hox function along the AP axis of the nephrogenic cord is critical for the differentiation and integration of these cell types during kidney organogenesis.
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影响因子：
11.8
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