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Genetic evidence that FGFs have an instructive role in limb proximal–distal patterning

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  • Francesca V. Mariani

    (School of Medicine, University of California at San Francisco, San Francisco, California 94158-2324, USA
    Present address: Broad Center for Stem Cell Research and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.)

  • Christina P. Ahn

    (School of Medicine, University of California at San Francisco, San Francisco, California 94158-2324, USA)

  • Gail R. Martin

    (School of Medicine, University of California at San Francisco, San Francisco, California 94158-2324, USA)

Abstract

Fibroblast growth factors in development The developing limb bud possesses a small ridge, the apical ectodermal ridge (AER), that produces signals controlling development of the limb along the proximal–distal axis (from the upper arms to the finger tips). Fibroblast growth factors (FGFs) are known to be key AER signals, but as four FGFs are expressed in the mouse AER, it has been difficult to understand their roles. Mariani et al. used genetic techniques to delete different combinations of FGFs from the mouse limb, thereby revealing the contribution made by each FGF to the total AER-FGF signal. Only one of the four AER-FGFs, Fgf8, was found to be essential for normal limb development. This dispels a longstanding notion that there is a positive feedback loop between the three other FGF genes expressed in the posterior AER and the sonic hedgehog gene. They also provide the first genetic evidence that the AER-FGFs serve as distalizing factors for establishing limb patterning, suggesting a role of FGFs as patterning molecules. They present a model that synthesizes the new findings with several other controversial papers published in recent years on the validity of the 'progress zone' versus the 'early specification' model of limb development.

Suggested Citation

  • Francesca V. Mariani & Christina P. Ahn & Gail R. Martin, 2008. "Genetic evidence that FGFs have an instructive role in limb proximal–distal patterning," Nature, Nature, vol. 453(7193), pages 401-405, May.
    • Handle: RePEc:nat:nature:v:453:y:2008:i:7193:d:10.1038_nature06876
    DOI: 10.1038/nature06876
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    Cited by:

    1. Catarina R. Oliveira & Dunja Knapp & Ahmed Elewa & Tobias Gerber & Sandra G. Gonzalez Malagon & Phillip B. Gates & Hannah E. Walters & Andreas Petzold & Hernan Arce & Rodrigo C. Cordoba & Elaiyaraja S, 2022. "Tig1 regulates proximo-distal identity during salamander limb regeneration," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Sofia Sedas Perez & Caitlin McQueen & Holly Stainton & Joseph Pickering & Kavitha Chinnaiya & Patricia Saiz-Lopez & Marysia Placzek & Maria A. Ros & Matthew Towers, 2023. "Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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