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doi: 10.1242/10.1242/dev.00537

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Development 130, 3515-3524 (2003)
Copyright © 2003 The Company of Biologists Limited

The zebrafish fgf24 mutant identifies an additional level of Fgf signaling involved in vertebrate forelimb initiation

Sabine Fischer1, Bruce W. Draper2 and Carl J. Neumann1,*

1 EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
2 Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, PO Box 19024, 1100 Fairview Avenue North, Seattle, WA 98109 USA

* Author for correspondence (e-mail: carl.neumann{at}embl-heidelberg.de)

Accepted 11 April 2003

The development of vertebrate limb buds is triggered in the lateral plate mesoderm by a cascade of genes, including members of the Fgf and Wnt families, as well as the transcription factor tbx5. Fgf8, which is expressed in the intermediate mesoderm, is thought to initiate forelimb formation by activating wnt2b, which then induces the expression of tbx5 in the adjacent lateral plate mesoderm. Tbx5, in turn, is required for the activation of fgf10, which relays the limb inducing signal to the overlying ectoderm. We show that the zebrafish fgf24 gene, which belongs to the Fgf8/17/18 subfamily of Fgf ligands, acts downstream of tbx5 to activate fgf10 expression in the lateral plate mesoderm. We also show that fgf24 activity is necessary for the migration of tbx5-expressing cells to the fin bud, and for the activation of shh, but not hand2, expression in the posterior fin bud.

Key words: Zebrafish, Limb development, fgf24, fgf10, tbx5, wnt2b, ikarus, Pectoral fin, Apical ectodermal ridge




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