FGF8 is essential for formation of the ductal system in the male reproductive tract
FGF8 is essential for formation of the ductal system in the male reproductive tract
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DOI：
10.1242/dev.051888
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发表时间：
2011-12-15
期刊：
影响因子：
4.6
通讯作者：
Perantoni, Alan O.
中科院分区：
文献类型：
--
作者：
Kitagaki, Jirouta;Ueda, Yutaka;Perantoni, Alan O.
在泌尿生殖道发育过程中，成纤维细胞生长因子8（Fgf 8）在中肾小管中表达，但其在该组织中的作用仍不明确。对先前产生的T-Cre介导的Fgf 8缺陷型小鼠（T-Cre; Fgf 8（flox/Delta 2，3）小鼠）（其在中胚层中缺乏Fgf 8表达）的评估揭示，沃尔夫管的颅侧区域过早退化并且颅侧中肾小管缺失。结果，突变小鼠的附睾、输精管和输出小管基本上缺失。Rarb 2-Cre用于从中肾小管消除FGF 8，但允许在相邻体节中表达。这些突变体保留了沃尔夫氏管的头端，并形成了附睾和输精管，但未能详细说明传出小管，表明Fgf 8表达的中肾小管是专门需要的小管的形成。Ret基因敲除小鼠不形成输尿管芽，这是沃尔夫氏管的尾部生长物和肾脏中集合管网络的祖细胞，但它们正常发育头端。这表明，Fgf 8，而不是Ret，表达是必不可少的颅中肾管从沃尔夫管的生长和男性生殖道中的性附属组织的主要部分的发展。从机制上讲，FGF 8在形成肾单位时在Lhx 1表达上游发挥作用，对Fgf 8突变体的分析同样显示中肾小管中Lhx 1表达缺陷。这些结果表明，在建立男性生殖道导管和牵连Lhx 1信号在小管伸长的FGF 8的多焦点需求。
During development of the urogenital tract, fibroblast growth factor 8 (Fgf8) is expressed in mesonephric tubules, but its role in this tissue remains undefined. An evaluation of previously generated T-Cre-mediated Fgf8-deficient mice (T-Cre; Fgf8(flox/Delta 2,3) mice), which lack Fgf8 expression in the mesoderm, revealed that the cranial region of the Wolffian duct degenerated prematurely and the cranial mesonephric tubules were missing. As a result, the epididymis, vas deferens and efferent ductules were largely absent in mutant mice. Rarb2-Cre was used to eliminate FGF8 from the mesonephric tubules but to allow expression in the adjacent somites. These mutants retained the cranial end of the Wolffian duct and formed the epididymis and vas deferens, but failed to elaborate the efferent ductules, indicating that Fgf8 expression by the mesonephric tubules is required specifically for the formation of the ductules. Ret knockout mice do not form the ureteric bud, a caudal outgrowth of the Wolffian duct and progenitor for the collecting duct network in the kidney, but they do develop the cranial end normally. This indicates that Fgf8, but not Ret, expression is essential to the outgrowth of the cranial mesonephric tubules from the Wolffian duct and to the development of major portions of the sex accessory tissues in the male reproductive tract. Mechanistically, FGF8 functions upstream of Lhx1 expression in forming the nephron, and analysis of Fgf8 mutants similarly shows deficient Lhx1 expression in the mesonephric tubules. These results demonstrate a multifocal requirement for FGF8 in establishing the male reproductive tract ducts and implicate Lhx1 signaling in tubule elongation.