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1: Science. 2004 Jul 16;305(5682):396-9.
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The limb bud Shh-Fgf feedback loop is terminated by expansion of former ZPA cells.

Scherz PJ, Harfe BD, McMahon AP, Tabin CJ.

Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Vertebrate limb outgrowth is driven by a positive feedback loop involving Sonic Hedgehog (Shh), Gremlin, and Fgf4. By overexpressing individual components of the loop at a time after these genes are normally down-regulated in chicken embryos, we found that Shh no longer maintains Gremlin in the posterior limb. Shh-expressing cells and their descendants cannot express Gremlin. The proliferation of these descendants forms a barrier separating the Shh signal from Gremlin-expressing cells, which breaks down the Shh-Fgf4 loop and thereby affects limb size and provides a mechanism explaining regulative properties of the limb bud.

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PMID: 15256670 [PubMed - indexed for MEDLINE]