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First published online 27 July 2005
doi: 10.1242/dev.01945

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.01945v1 132/17/3859    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perantoni, A. O. Articles by Lewandoski, M. Search for Related Content PubMed PubMed Citation Articles by Perantoni, A. O. Articles by Lewandoski, M.

Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development

Alan O. Perantoni¹, Olga Timofeeva^1,*, Florence Naillat^3,*, Charmaine Richman², Sangeeta Pajni-Underwood², Catherine Wilson², Seppo Vainio³, Lee F. Dove¹ and Mark Lewandoski^2,

¹ Laboratory of Comparative Carcinogenesis, National Cancer Institute, NCI-Frederick, Frederick, MD 21702, USA
² Cancer and Developmental Biology Laboratory, National Cancer Institute, NCI-Frederick, Frederick, MD 21702, USA
³ Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, PO Box 5000, FIN-90014 Oulu, Finland

Author for correspondence (e-mail: mlewandoski{at}mail.ncifcrf.gov)

Accepted 17 June 2005

To bypass the essential gastrulation function of Fgf8 and study its role in lineages of the primitive streak, we have used a new mouse line, T-Cre, to generate mouse embryos with pan-mesodermal loss of Fgf8 expression. Surprisingly, despite previous models in which Fgf8 has been assigned a pivotal role in segmentation/somite differentiation, Fgf8 is not required for these processes. However, mutant neonates display severe renal hypoplasia with deficient nephron formation. In mutant kidneys, aberrant cell death occurs within the metanephric mesenchyme (MM), particularly in the cortical nephrogenic zone, which provides the progenitors for recurring rounds of nephron formation. Prior to mutant morphological changes, Wnt4 and Lim1 expression, which is essential for nephrogenesis, is absent in MM. Furthermore, comparative analysis of Wnt4-null homozygotes reveals concomitant downregulation of Lim1 and diminished tubule formation. Our data support a model whereby FGF8 and WNT4 function in concert to induce the expression of Lim1 for MM survival and tubulogenesis.

Key words: Cre recombinase, Fgf8, Kidney, Lim1, Nephron, Somitogenesis, T-Cre, Wnt4, Mouse

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Development 2005 132: e1702. [Full Text]  

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