Molecular analysis of external genitalia formation: the role of fibroblast growth factor (Fgf) genes during genital tubercle formation.
Molecular analysis of external genitalia formation: the role of fibroblast growth factor (Fgf) genes during genital tubercle formation.
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发表时间：
2000-06
期刊：
影响因子：
4.6
通讯作者：
R. Haraguchi;Kentarou Suzuki;R. Murakami;M. Sakai;M. Kamikawa;M. Kengaku;K. Sekine;Hirotaka Kawano;S. Kato;N. Ueno;G. Yamada
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文献类型：
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作者：
R. Haraguchi;Kentarou Suzuki;R. Murakami;M. Sakai;M. Kamikawa;M. Kengaku;K. Sekine;Hirotaka Kawano;S. Kato;N. Ueno;G. Yamada
哺乳动物外生殖器发育的分子机制很少被研究。最近的基因敲除研究表明，它的原基，生殖结节（GT）的发育过程中，有许多共同的肢体芽。Fgf基因已被假定为在器官发生过程中调节几个下游基因。Fgf 8在生殖结节（GT）的远端尿道板上皮中表达，其他标记物如Msx 1、Fgf 10、Hoxd 13和Bmp 4在间充质中表达。为了分析GT形成过程中FGF系统的作用，利用体外器官培养系统。提示GT的远端尿道板上皮是FGF 8的表达区域，调节GT的生长。异位应用FGF 8珠粒诱导小鼠GT间充质基因表达，也促进GT的生长。利用抗FGF中和抗体的实验提示FGF蛋白在GT生长中具有生长促进作用。相比之下，尽管它在肢芽形成过程中的重要作用，Fgf 10似乎不是主要的GT的初始生长所必需的，从Fgf 10（-/-）GT外推。而Fgf 10（-/-）围产期小鼠外生殖器发育异常提示Fgf 10在阴茎头和阴蒂头发育中的重要性。这些结果表明，FGF系统是协调GT发展的关键因素。
The molecular mechanisms underlying the development of the external genitalia in mammals have been very little examined. Recent gene knockout studies have suggested that the developmental processes of its anlage, the genital tubercle (GT), have much in common with those of limb buds. The Fgf genes have been postulated as regulating several downstream genes during organogenesis. Fgf8 was expressed in the distal urethral plate epithelium of the genital tubercle (GT) together with other markers such as the Msx1, Fgf10, Hoxd13 and Bmp4 expressed in the mesenchyme. To analyze the role of the FGF system during GT formation, an in vitro organ culture system was utilized. It is suggested that the distal urethral plate epithelium of GT, the Fgf8-expressing region, regulates the outgrowth of GT. Ectopic application of FGF8 beads to the murine GT induced mesenchymal gene expression, and also promoted the outgrowth of the GT. Experiments utilizing anti-FGF neutralizing antibody suggested a growth-promoting role for FGF protein(s) in GT outgrowth. In contrast, despite its vital role during limb-bud formation, Fgf10 appears not to be primarily essential for initial outgrowth of GT, as extrapolated from Fgf10(-/-) GTs. However, the abnormal external genitalia development of Fgf10(-/-) perinatal mice suggested the importance of Fgf10 in the development of the glans penis and the glans clitoridis. These results suggest that the FGF system is a key element in orchestrating GT development.