Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

中文翻译：

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Hox9,10,11功能的破坏导致肾脏中细胞水平谱系的不忠。

Hox基因是重要的发育调节因子。39个哺乳动物的Hox基因具有相当大的功能重叠，这极大地混淆了他们的研究。在此报告中，我们生成了具有多个旁系同源和侧翼Abd-B Hox基因突变组合的小鼠，以研究肾脏发育中的功能冗余。生成的小鼠出现了许多肾脏异常，包括发育不全，发育不全和严重的囊肿，在早期后肾形成和肾祖细胞维持中观察到了明显的Hox功能。然而，最令人惊讶的是，这些肾脏中Hox共有功能的广泛去除导致细胞水平谱系不忠。引人注目的是，突变肾单位肾小管由混合细胞与近端肾小管，Henle环和收集管道的特征组成，一些单细胞表达与一个以上肾单位段相关的标记。这些结果表明，Hox基因是适当的谱系选择/维持和发育中肾脏细胞命运限制相关基因的完全抑制所必需的。