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Science 332 (6033): 1038-1039

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

Limb Cells Don't Tell Time

Susan Mackem, and Mark Lewandoski

Although limb development is one of the best models to study pattern formation and morphogenesis, the mechanisms that control its sequential proximal-to-distal, shoulder to finger tip formation have remained controversial (1). According to the "progress zone" model, limb progenitor cells become progressively "distalized" in identity via an internal clock mechanism that tracks time spent under the influence of permissive fibroblast growth factor (FGF) signals from the distal limb bud margin, although recent work has challenged this idea (2). Alternative models propose that proximal signals could instruct proximal-distal cell fate, obviating the need for a cell-autonomous clock. Two papers in this issue, by Cooper et al. (3) on page 1083 and Roselló-Díez et al. (4) on page 1086, support the latter model and show that the dynamic balance between proximal retinoic acid (RA) signaling and distal FGF activity governs the proximal-distal pattern of major limb segments in the chick. Combined signals also maintain the proximal-distal plasticity and progenitor state of limb bud cells. These signaling roles in limb development are reminiscent of events during limb regeneration, suggesting a higher level of parsimony between the two than once thought.

Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.

E-mail: mackems{at}, lewandom{at}

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