Di-Poï Nicolas, Zákány József, Duboule Denis
Department of Zoology and Animal Biology, University of Geneva, Geneva, Swizerland.
PLoS Genet. 2007 Dec;3(12):e232. doi: 10.1371/journal.pgen.0030232.
Hox genes encode homeodomain-containing proteins that control embryonic development in multiple contexts. Up to 30 Hox genes, distributed among all four clusters, are expressed during mammalian kidney morphogenesis, but functional redundancy between them has made a detailed functional account difficult to achieve. We have investigated the role of the HoxD cluster through comparative molecular embryological analysis of a set of mouse strains carrying targeted genomic rearrangements such as deletions, duplications, and inversions. This analysis allowed us to uncover and genetically dissect the complex role of the HoxD cluster. Regulation of metanephric mesenchyme-ureteric bud interactions and maintenance of structural integrity of tubular epithelia are differentially controlled by some Hoxd genes during renal development, consistent with their specific expression profiles. We also provide evidence for a kidney-specific form of colinearity that underlies the differential expression of two distinct sets of genes located on both sides and overlapping at the Hoxd9 locus. These insights further our knowledge of the genetic control of kidney morphogenesis and may contribute to understanding certain congenital kidney malformations, including polycystic kidney disease and renal hypoplasia.
Hox基因编码含同源结构域的蛋白质，这些蛋白质在多种情况下控制胚胎发育。在哺乳动物肾脏形态发生过程中，分布于所有四个基因簇中的多达30个Hox基因会表达，但它们之间的功能冗余使得难以实现详细的功能描述。我们通过对一组携带靶向基因组重排（如缺失、重复和倒位）的小鼠品系进行比较分子胚胎学分析，研究了HoxD基因簇的作用。该分析使我们能够揭示并从遗传学角度剖析HoxD基因簇的复杂作用。在肾脏发育过程中，一些Hoxd基因对后肾间充质-输尿管芽相互作用的调节以及肾小管上皮结构完整性的维持具有不同的控制作用，这与其特定的表达谱一致。我们还提供了一种肾脏特异性共线性形式的证据，这种共线性是位于Hoxd9基因座两侧且重叠的两组不同基因差异表达的基础。这些见解加深了我们对肾脏形态发生遗传控制的认识，并可能有助于理解某些先天性肾脏畸形，包括多囊肾病和肾发育不全。
