Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung.
Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung.
复制标题
DOI：
10.1002/dvdy.22032
复制
发表时间：
2009-08
影响因子：
2.5
通讯作者：
Sun, Xin
中科院分区：
文献类型：
--
作者：
Abler, Lisa L.;Mansour, Suzanne L.;Sun, Xin
成纤维细胞生长因子10（FGF 10）通过FGF受体2（FGFR 2）的信号传导是肺启动所需的。虽然研究表明Fgf 10和Fgfr 2在肺发育的后期也很重要，但它们在早期分支事件中的作用仍不清楚。我们通过在小鼠肺启动后条件性失活这两个基因来解决这个问题。肺间充质中Fgf 10的失活导致较小的肺叶和减少的分支数量。肺上皮中Fgfr 2的失活导致肺叶破坏和沿主支气管任意沿着出现的小上皮增生。在这两种突变体中，细胞死亡都有所增加。此外，分支形态发生中涉及的关键信号分子的表达模式被改变，近端肺标记物向远端扩展。我们的研究结果表明，FGF 10和FGFR 2都需要一个正常的分支程序和适当的近端-远端模式的肺。
Fibroblast growth factor 10 (FGF10) signaling through FGF receptor 2 (FGFR2) is required for lung initiation. While studies indicate that Fgf10 and Fgfr2 are also important at later stages of lung development, their roles in early branching events remain unclear. We addressed this question through conditional inactivation of both genes in mouse subsequent to lung initiation. Inactivation of Fgf10 in lung mesenchyme resulted in smaller lobes with a reduced number of branches. Inactivation of Fgfr2 in lung epithelium resulted in disruption of lobes and small epithelial outgrowths that arose arbitrarily along the main bronchi. In both mutants, there was an increase in cell death. Also, the expression patterns of key signaling molecules implicated in branching morphogenesis were altered and a proximal lung marker was expanded distally. Our results indicate that both Fgf10 and Fgfr2 are required for a normal branching program and for proper proximal-distal patterning of the lung.
登录
查看更多内容
影响因子：
2.6
作者：
MASON, IJ;FULLERPACE, F;DICKSON, C
通讯作者：
DICKSON, C
影响因子：
64.8
作者：
GURDON, JB
通讯作者：
GURDON, JB
影响因子：
4.6
作者：
Mailleux, AA;Kelly, R;Bellusci, S
通讯作者：
Bellusci, S
DOI：
10.1073/pnas.95.9.5082
发表时间：
1998-04-28
影响因子：
11.1
作者：
Arman, E;Haffner-Krausz, R;Lonai, P
通讯作者：
Lonai, P
影响因子：
1.2
作者：
Liu, Yuru;Hogan, Brigid L. M.
通讯作者：
Hogan, Brigid L. M.