Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development.
Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development.
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DOI：
10.1002/dvdy.22501
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发表时间：
2011-01
影响因子：
2.5
通讯作者：
Bates, Carlton M.
中科院分区：
文献类型：
--
作者：
Sims-Lucas, Sunder;Cusack, Brian;Baust, Jeffrey;Eswarakumar, Veraragavan P.;Masatoshi, Hagiwara;Takeuchi, Akihide;Bates, Carlton M.
成纤维细胞生长因子受体（Fgfrs）在肾脏发育中具有关键作用。FgfrIIIb被认为在上皮中起作用，而FgfrIIIc在间充质中起作用。我们的目的是确定Fgfr 2 IIIc在肾脏发育中的作用。Fgfr 2 IIIc缺失的小鼠（Fgfr 2 IIIc −/−）有正常的肾脏。后肾间充质（MM）中Fgfr 2 IIIc −/−与Fgfr 1条件性缺失的组合（Fgfr 1 Mes −/− Fgfr 2 IIIc −/−）在E10.5时具有小但可识别的MM，表达间充质标志物，包括Eya 1，Six 2，Pax 2和Gdnf（不像Fgfr 1/2 Mes −/−小鼠没有明显的MM）。E11.5 Fgfr 1 Mes −/− Fgfr 2 IIIc −/−小鼠具有仅表达Eya 1的基本MM。对照、Fgfr 2 IIIc −/−和Fgfr 1 Mes −/− Fgfr 2 IIIc −/−肾间充质组织也表达Fgfr 2 IIIb。在输尿管谱系中，E10.5 Fgfr 1 Mes −/− Fgfr 2 IIIc −/−胚胎有输尿管生长（有时多个芽）;然而，E11.5 Gdnf缺失导致输尿管不伸长或分支（类似于Fgfr 1/2 Mes −/−小鼠）。超过E12.5，Fgfr 1 Mes −/− Fgfr 2 IIIc −/−小鼠没有肾组织。总之，肾间质中的Fgfr 2 IIIc和Fgfr 1（一起）对于正常的早期肾脏发育至关重要。
Fibroblast growth factor receptors (Fgfrs) have critical roles in kidney development. FgfrIIIb is thought to act in epithelium, while FgfrIIIc functions in mesenchyme. We aimed to determine roles of Fgfr2IIIc in kidney development. Mice with deletion of Fgfr2IIIc (Fgfr2IIIc−/−) had normal kidneys. Combination of Fgfr2IIIc−/− with conditional deletion of Fgfr1 in metanephric mesenchyme (MM) (Fgfr1Mes−/−Fgfr2IIIc−/−) had small but identifiable MM at E10.5, expressing mesenchymal markers including Eya1, Six2, Pax2 and Gdnf (unlike Fgfr1/2Mes−/− mice that have no obvious MM). E11.5 Fgfr1Mes−/−Fgfr2IIIc−/− mice had rudimentary MM expressing only Eya1. Control, Fgfr2IIIc−/−, and Fgfr1Mes−/−Fgfr2IIIc−/− kidney mesenchymal tissues also express Fgfr2IIIb. In ureteric lineages, E10.5 Fgfr1Mes−/−Fgfr2IIIc−/− embryos had ureteric outgrowth (sometimes multiple buds); however, by E11.5 Gdnf absence lead to no ureteric elongation or branching (similar to Fgfr1/2Mes−/− mice). Beyond E12.5, Fgfr1Mes−/−Fgfr2IIIc−/− mice had no renal tissue. In conclusion, Fgfr2IIIc and Fgfr1 in kidney mesenchyme (together) are critical for normal early renal development.
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