The Limb Bud Shh-Fgf Feedback Loop Is Terminated by Expansion of Former ZPA Cells

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 post...

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Veröffentlicht in:Science (American Association for the Advancement of Science) 2004-07, Vol.305 (5682), p.396-399
Hauptverfasser: Scherz, Paul J., Harfe, Brian D., McMahon, Andrew P., Tabin, Clifford J.
Format: Artikel
Sprache:eng
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Zusammenfassung: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1096966