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Developmental Biology
Article
License: Elsevier Non-Commercial
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Developmental Biology
Article . 2008
License: Elsevier Non-Commercial
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Developmental Biology
Article . 2008 . Peer-reviewed
License: Elsevier Non-Commercial
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Disp1 regulates growth of mammalian long bones through the control of Ihh distribution

Authors: Tsiairis, Charisios D.; McMahon, Andrew P.;

Disp1 regulates growth of mammalian long bones through the control of Ihh distribution

Abstract

Dispatched1 (Disp1) is required for the release of cholesterol modified hedgehog (Hh) proteins from producing cells. We investigated the role of Disp1 in Indian hedgehog (Ihh) signaling in the developing bone bypassing the lethality of the Disp1(C829F) allele at early somite stages through the supply of non-cholesterol modified Sonic hedgehog (N-Shh). The long bones that develop in the absence of wild-type Disp1, while clearly shorter, have a juxtaposition of proliferating and non-proliferating hypertrophic chondrocytes that is markedly more normal in organization than those of ihh null mutants. Direct analysis of Ihh trafficking in the target field demonstrates that Ihh is distributed well beyond Ihh expressing cells though the range of movement and signaling action is more restricted than in wild-type long bones. Consequently, a PTHrP-Ihh feedback loop is established, but over a shorter distance, reflecting the reduced range of Ihh movement. These analyses of the Disp1(C829F) mutation demonstrate that Disp1 is not absolutely required for the paracrine signaling role of Ihh in the skeleton. However, Disp1 is critical for the full extent of signaling within the chondrocyte target field and consequently the establishment of a normal skeletal growth plate.

Related Organizations
Keywords

Bone Development, PTHrP, Endochondral ossification, Membrane Proteins, Cell Biology, Ihh gradient, Mice, Bromodeoxyuridine, Mutation, Growth plate, Animals, Hedgehog Proteins, Disp1, Molecular Biology, In Situ Hybridization, Developmental Biology, Signal Transduction

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selected citations
These citations are derived from selected sources.
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!
12
Average
Average
Average
hybrid