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Fgf8 is required for outgrowth and patterning of the limbs

Nature Genetics volume 26, pages 455–459 (2000)Cite this article

Abstract

The expression pattern and activity of fibroblast growth factor-8 (FGF8) in experimental assays indicate that it has important roles in limb development1,2,3, but early embryonic lethality resulting from mutation of Fgf8 in the germ line of mice has prevented direct assessment of these roles4. Here we report that conditional disruption of Fgf8 in the forelimb of developing mice bypasses embryonic lethality and reveals a requirement for Fgf8 in the formation of the stylopod, anterior zeugopod and autopod. Lack of Fgf8 in the apical ectodermal ridge (AER) alters expression of other Fgf genes, Shh and Bmp2.

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Figure 1: Targeting the Fgf8 locus.
Figure 2: Fgf8 expression and alkaline phosphatase activity in embryos bearing mutant alleles of Fgf8.
Figure 3: Morphology of Fgf8 conditional mutants.
Figure 4: Fgf8 regulates Fgf4 expression in the AER.
Figure 5: Abnormal morphology and outgrowth of Fgf8 conditional mutant forelimb buds results from increased apoptosis and decreased Fgf10 expression.
Figure 6: Shh expression is not maintained in the ZPA of Fgf8 conditional mutants, but asymmetry of Bmp2 expression is preserved.

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Acknowledgements

We thank J. Tomlin for technical assistance; vivarium staff for their ongoing efforts; members of the Capecchi laboratory for input and critical reading of the manuscript; L. Oswald for assistance with preparing the manuscript; A. McMahon, B. Hogan, C. Deng and D. Ornitz for in situ probes; and J. Deschamps for the RAR β2 promoter fragment.

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Authors and Affiliations

  1. Departments of Pediatrics and Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA

    Anne M. Moon

  2. Howard Hughes Medical Institute and Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA

    Mario R. Capecchi

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  1. Anne M. Moon
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Correspondence to Mario R. Capecchi.

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Moon, A., Capecchi, M. Fgf8 is required for outgrowth and patterning of the limbs. Nat Genet 26, 455–459 (2000). https://doi.org/10.1038/82601

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