The murine Fgfrl1 receptor is essential for the development of the metanephric kidney
The murine Fgfrl1 receptor is essential for the development of the metanephric kidney
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DOI：
10.1016/j.ydbio.2009.08.019
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发表时间：
2009-11-01
影响因子：
2.7
通讯作者：
Trueb, Beat
中科院分区：
文献类型：
--
作者：
Gerber, Simon D.;Steinberg, Florian;Trueb, Beat
Fgfrl 1是成纤维细胞生长因子受体家族的新成员。其细胞外结构域类似于四种常规的Fgfr，而其细胞内结构域缺乏FGF介导的信号转导所必需的酪氨酸激酶结构域。在胚胎发育期间，Fgfrl 1在肌肉骨骼系统、肺、胰腺和后肾中表达。有针对性地破坏Fgfrl 1基因会导致小鼠因隔膜发育不良而导致围产期死亡，隔膜无法使肺部充气。在这里，我们发现Fgfrl 1-/-胚胎也不能发育后肾。虽然泌尿生殖系统的其余部分，包括膀胱、输尿管和性器官，发育正常，但输尿管分支形态发生的急剧减少和肾源性间充质中间充质至上皮转化的缺乏导致严重的肾发育不全。肾单位诱导的失败可能是由于突变动物在E12.5时缺乏小管形成标记物Wnt 4、Fgf 8、Pax 8和Lim 1。我们还观察到Pax 2阳性肾单位前体细胞的丢失和残肾皮质区细胞凋亡的增加。因此，Fgfrl 1是肾发生早期间充质分化所必需的。(C)2009 Elsevier Inc. All rights reserved.
Fgfrl1 is a novel member of the fibroblast growth factor receptor family. Its extracellular domain resembles the four conventional Fgfrs, while its intracellular domain lacks the tyrosine kinase domain necessary for Fgf mediated signal transduction. During embryonic development Fgfrl1 is expressed in the musculoskeletal system, in the lung, the pancreas and the metanephric kidney. Targeted disruption of the Fgfrl1 gene leads to the perinatal death of the mice due to a hypoplastic diaphragm, which is unable to inflate the lungs. Here we show that Fgfrl1-/- embryos also fail to develop the metanephric kidney. While the rest of the urogenital system, including bladder, ureter and sexual organs, develops normally, a dramatic reduction of ureteric branching morphogenesis and a lack of mesenchymal-to-epithelial transition in the nephrogenic mesenchyme result in severe renal dysgenesis. The failure of nephron induction might be explained by the absence of the tubulogenic markers Wnt4, Fgf8, Pax8 and Lim1 at E12.5 of the mutant animals. We also observed a loss of Pax2 positive nephron precursor cells and an increase of apoptosis in the cortical zone of the remnant kidney. Fgfrl1 is therefore essential for mesenchymal differentiation in the early steps of nephrogenesis. (C) 2009 Elsevier Inc. All rights reserved.