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Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development
Author(s) -
SimsLucas Sunder,
Cusack Brian,
Baust Jeffrey,
Eswarakumar Veraragavan P.,
Masatoshi Hagiwara,
Takeuchi Akihide,
Bates Carlton M.
Publication year - 2011
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22501
Subject(s) - mesenchyme , kidney development , fibroblast growth factor receptor 1 , glial cell line derived neurotrophic factor , biology , kidney , fibroblast growth factor , fibroblast growth factor receptor , medicine , microbiology and biotechnology , endocrinology , embryonic stem cell , mesenchymal stem cell , receptor , genetics , gene , neurotrophic factors
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) ( Fgfr1 Mes−/− Fgfr2IIIc−/− ) had small but identifiable MM at embryonic day (E) 10.5, expressing mesenchymal markers including Eya1 , Six2 , Pax2 , and Gdnf (unlike Fgfr1/2 Mes−/− mice that have no obvious MM). E11.5 Fgfr1 Mes−/− Fgfr2IIIc−/− mice had rudimentary MM expressing only Eya1 . Control, Fgfr2IIIc−/− , and Fgfr1 Mes−/− Fgfr2IIIc−/− kidney mesenchymal tissues also express Fgfr2IIIb . In ureteric lineages, E10.5 Fgfr1 Mes−/− Fgfr2IIIc−/− embryos had ureteric outgrowth (sometimes multiple buds); however, by E11.5 Gdnf absence lead to no ureteric elongation or branching (similar to Fgfr1/2 Mes−/− mice). Beyond E12.5, Fgfr1 Mes−/− Fgfr2IIIc−/− mice had no renal tissue. In conclusion, Fgfr2IIIc and Fgfr1 in kidney mesenchyme (together) are critical for normal early renal development. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.