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Cell
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Cell
Article . 2004
License: Elsevier Non-Commercial
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Dynamic Changes in the Response of Cells to Positive Hedgehog Signaling during Mouse Limb Patterning

Authors: Alexandra L. Joyner; Alexandra L. Joyner; Sohyun Ahn;

Dynamic Changes in the Response of Cells to Positive Hedgehog Signaling during Mouse Limb Patterning

Abstract

In the vertebrate limb, the posteriorly located zone of polarizing activity (ZPA) regulates digit identity through the morphogen Sonic Hedgehog (Shh). By genetically marking Shh-responding cells in mice, we have addressed whether the cumulative influence of positive Shh signaling over time and space reflects a linear gradient of Shh responsiveness and whether Shh could play additional roles in limb patterning. Our results show that all posterior limb mesenchyme cells, as well as the ectoderm, respond to Shh from the ZPA and become the bone, muscle, and skin of the posterior limb. Further, the readout of Shh activator function integrated over time and space does not display a stable and linear gradient along the A-P axis, as in a classical morphogen view. Finally, by fate mapping Shh-responding cells in Gli2 and Gli3 mutant limbs, we demonstrate that a specific level of positive Hh signaling is not required to specify digit identities.

Related Organizations
Keywords

Mice, Knockout, DNA, Complementary, Models, Genetic, Biochemistry, Genetics and Molecular Biology(all), Blotting, Western, Kruppel-Like Transcription Factors, Down-Regulation, Gene Expression Regulation, Developmental, Extremities, Nerve Tissue Proteins, Models, Biological, DNA-Binding Proteins, Blotting, Southern, Mice, Mutation, Animals, Cell Lineage, Hedgehog Proteins, Alleles, In Situ Hybridization, Body Patterning

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    475
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 1%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
475
Top 1%
Top 1%
Top 1%
hybrid