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Science 332 (6033): 1083-1086

Copyright © 2011 by the American Association for the Advancement of Science

Initiation of Proximal-Distal Patterning in the Vertebrate Limb by Signals and Growth

Kimberly L. Cooper,1,* Jimmy Kuang-Hsien Hu,1,* Derk ten Berge,2 Marian Fernandez-Teran,3 Maria A. Ros,3 Clifford J. Tabin1,{dagger}

Abstract: Two broad classes of models have been proposed to explain the patterning of the proximal-distal axis of the vertebrate limb (from the shoulder to the digit tips). Differentiating between them, we demonstrate that early limb mesenchyme in the chick is initially maintained in a state capable of generating all limb segments through exposure to a combination of proximal and distal signals. As the limb bud grows, the proximal limb is established through continued exposure to flank-derived signal(s), whereas the developmental program determining the medial and distal segments is initiated in domains that grow beyond proximal influence. In addition, the system we have developed, combining in vitro and in vivo culture, opens the door to a new level of analysis of patterning mechanisms in the limb.

1 Harvard Medical School, Department of Genetics, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
2 Erasmus Medical Center, Erasmus MC Stem Cell Institute, Department of Cell Biology, Post Office Box 2040, 3000 CA Rotterdam, Netherlands.
3 Universidad de Cantabria Instituto de Biomedicina y Biotecnologia (CSIC-UC-IDICAN), C/ Herrera Oria s/n, E-39011 Santander, Spain.

* These authors contributed equally to this work.

{dagger} To whom correspondence and requests for materials should be addressed. E-mail: tabin{at}

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