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Science 22 May 1998:
Vol. 280. no. 5367, pp. 1274 - 1277
DOI: 10.1126/science.280.5367.1274
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Reports

Distinct WNT Pathways Regulating AER Formation and Dorsoventral Polarity in the Chick Limb Bud

Mineko Kengaku, *dagger Javier Capdevila, * Concepción Rodriguez-Esteban, * Jennifer De La Peña, Randy L. Johnson, Juan Carlos Izpisúa Belmonte, ddagger § Clifford J. Tabin §

The apical ectodermal ridge (AER) is an essential structure for vertebrate limb development. Wnt3a is expressed during the induction of the chick AER, and misexpression of Wnt3a induces ectopic expression of AER-specific genes in the limb ectoderm. The genes beta -catenin and Lef1 can mimic the effect of Wnt3a, and blocking the intrinsic Lef1 activity disrupts AER formation. Hence, Wnt3a functions in AER formation through the beta -catenin/LEF1 pathway. In contrast, neither beta -catenin nor Lef1 affects the Wnt7a-regulated dorsoventral polarity of the limb. Thus, two related Wnt genes elicit distinct responses in the same tissues by using different intracellular pathways.

M. Kengaku and C. J. Tabin, Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
J. Capdevila, C. Rodriguez-Esteban, J. De La Peña, J. C. I. Belmonte, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
R. L. Johnson, Department of Biochemistry and Molecular Biology, M.D. Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
*   These authors contributed equally to this work.

dagger    Present address: Department of Biophysics, Kyoto University, Sakyo-ku, Kyoto 606, Japan.

ddagger    To whom correspondence should be addressed. E-mail: belmonte{at}salk.edu

§   The laboratories of these authors contributed equally to this study.

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