Pax-2 controls multiple steps of urogenital development.
Pax-2 controls multiple steps of urogenital development.
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DOI：
10.1242/dev.121.12.4057
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发表时间：
1995-12
期刊：
影响因子：
4.6
通讯作者：
M. Torres;Emilia Gómez-Pardo;G. Dressler;Peter Gruss
中科院分区：
文献类型：
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作者：
M. Torres;Emilia Gómez-Pardo;G. Dressler;Peter Gruss
哺乳动物的泌尿生殖系统发育需要两种不同组织的协调分化，即导管上皮和肾间充质，两者都来自早期胚胎的中间中胚层。前者产生生殖道、输尿管和肾集合管系统，而间充质组分经历上皮转化以在中肾（胚胎）和后肾（定形）肾中形成肾单位。Pax-2是配对盒家族的转录调节因子，在泌尿生殖系统的导管和间充质组分的发育过程中广泛表达。我们在这里报告，Pax-2纯合子突变的新生小鼠缺乏肾脏，输尿管和生殖道。我们将这些缺陷归因于发育中的泌尿生殖系统的导管和间充质成分的发育不良。Wolffian和Müllerian导管分别是男性和女性生殖道的前体，在胚胎发育期间仅部分发育并退化。输尿管、后肾的诱导物不存在，因此肾脏不发育。生肾索的间质不能进行上皮转化，不能在中肾形成小管。此外，我们表明，这些组件中的每一个的特定标志物的表达是失调的Pax-2突变体。这些数据表明Pax-2是中间中胚层分化过程中多个步骤所必需的。此外，Pax-2小鼠突变体为人类遗传性肾病提供了动物模型。
Urogenital system development in mammals requires the coordinated differentiation of two distinct tissues, the ductal epithelium and the nephrogenic mesenchyme, both derived from the intermediate mesoderm of the early embryo. The former give rise to the genital tracts, ureters and kidney collecting duct system, whereas mesenchymal components undergo epithelial transformation to form nephrons in both the mesonephric (embryonic) and metanephric (definitive) kidney. Pax-2 is a transcriptional regulator of the paired-box family and is widely expressed during the development of both ductal and mesenchymal components of the urogenital system. We report here that Pax-2 homozygous mutant newborn mice lack kidneys, ureters and genital tracts. We attribute these defects to dysgenesis of both ductal and mesenchymal components of the developing urogenital system. The Wolffian and Müllerian ducts, precursors of male and female genital tracts, respectively, develop only partially and degenerate during embryogenesis. The ureters, inducers of the metanephros are absent and therefore kidney development does not take place. Mesenchyme of the nephrogenic cord fails to undergo epithelial transformation and is not able to form tubules in the mesonephros. In addition, we show that the expression of specific markers for each of these components is de-regulated in Pax-2 mutants. These data show that Pax-2 is required for multiple steps during the differentiation of intermediate mesoderm. In addition, Pax-2 mouse mutants provide an animal model for human hereditary kidney diseases.