Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Division
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Chick Embryo
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Cytokines
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Down-Regulation
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Feedback, Physiological
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Fibroblast Growth Factor 4
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Fibroblast Growth Factor 8
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Fibroblast Growth Factor 9
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Fibroblast Growth Factors / genetics
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Fibroblast Growth Factors / metabolism*
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Gene Expression Regulation, Developmental
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Hedgehog Proteins
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism*
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Limb Buds / cytology
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Limb Buds / embryology*
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Limb Buds / metabolism
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Mesoderm / cytology*
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Mesoderm / metabolism
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Mice
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Models, Biological
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Signal Transduction
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Trans-Activators / metabolism*
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Up-Regulation
Substances
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Cktsf1b1 protein, mouse
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Cytokines
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Fgf17 protein, mouse
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Fgf4 protein, mouse
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Fgf8 protein, mouse
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Fgf9 protein, mouse
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Fibroblast Growth Factor 4
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Fibroblast Growth Factor 9
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Hedgehog Proteins
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Intercellular Signaling Peptides and Proteins
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Proto-Oncogene Proteins
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Shh protein, mouse
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Trans-Activators
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Fibroblast Growth Factor 8
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Fibroblast Growth Factors