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

Francesca V. Mariani, Christina P. Ahn and Gail R. Martin ()
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Francesca V. Mariani: School of Medicine, University of California at San Francisco, San Francisco, California 94158-2324, 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

Nature, 2008, vol. 453, issue 7193, 401-405

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.

Date: 2008
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DOI: 10.1038/nature06876

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