Fibroblast growth factor 10 (Fgf10) invalidation results in anorectal malformation in mice
Fibroblast growth factor 10 (Fgf10) invalidation results in anorectal malformation in mice
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DOI：
10.1016/j.jpedsurg.2003.11.034
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发表时间：
2004-03-01
影响因子：
2.4
通讯作者：
Burns, RC
中科院分区：
文献类型：
--
作者：
Fairbanks, TJ;De Langhe, S;Burns, RC
背景/目的：每4，000例活产婴儿中就有1例发生肛门直肠畸形，这对手术来说是一个挑战。虽然至关重要，但正常肛门直肠愈合的基本机制尚未完全了解。已知Fgf 10信号传导在包括胃肠道（GIT）在内的许多器官系统中的间充质/上皮相互作用中起关键作用。因此，作者假设Fgf 10信号传导在正常肛门直肠发育中具有核心作用。方法：使用整装原位杂交评估野生型（Wt）胚胎中Fgf 10的表达，从E12.5至E17.5的定时妊娠母亲收获Wt和Fgf 10（-/-）胚胎，并分析肛门直肠表型。E12.5至E13.5之间肛门直肠结构之间的愈合完成，远端直肠上皮和肛门之间有管腔连通。Fgf 10在E12.5在远端直肠中谨慎表达。Fgf 10（-/-）突变体在早期（E13.5）和近期（E17.5）表现为直肠肛门愈合失败。结论：Fgf 10在肛门直肠连续性建立时在直肠表达，提示其在正常肛门直肠发育中起作用。Fgf 10失效（Fgf 10（-/-）突变体）导致遗传上可重复的肛门直肠畸形表型。fgf 10的功能对肛门直肠的正常发育至关重要。
Background/Purpose: Anorectal malformations occur in 1 per 4,000 live births and represent a surgical challenge. Although critically important, the basic mechanisms of normal anorectal union are incompletely understood. Fgf10 signaling is known to serve a key role in mesenchymal/epithelial interactions in many organ systems including the gastrointestinal tract (GIT). The authors therefore hypothesized that Fgf10 signaling has a central role in normal anorectal development.Methods: Fgf10 expression in wild-type (Wt) embryos was evaluated using whole-mount in situ hybridization, Wt and Fgf10(-/-) embryos were harvested from timed pregnant mothers at E12.5 through E17.5 and were analyzed for anorectal phenotype.Results: Wt development of union between anorectal structures is completed between E12.5 and E13.5 with luminal communication between distal rectal epithelium and anus. Fgf10 is discreetly expressed at E12.5 in the distal rectum. Fgf10(-/-) mutants show failure of union of the rectum and anus at an early stage (E13.5) and near term (E17.5).Conclusions: Fgf10 is expressed in the rectum at the time when anorectal continuity is established, indicating a role in normal anorectal development. Fgf10 invalidation (Fgf10(-/-) mutant) results in a genetically reproducible anorectal malformation phenotype. Fgf10 function is critical for normal anorectal development.