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Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signaling

The distribution of Sonic Hedgehog (Shh) is a highly regulated and critical process for development. Several negative feedback mechanisms are in place, including the Shh-induced upregulation of Hedgehog interacting protein (Hhip). Hhip sequesters Shh, leading to a non-cell autonomous inhibition of t...

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Detalles Bibliográficos
Autores principales: Kwong, Lina, Bijlsma, Maarten F., Roelink, Henk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163939/
https://www.ncbi.nlm.nih.gov/pubmed/25215859
http://dx.doi.org/10.1038/ncomms5849
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author Kwong, Lina
Bijlsma, Maarten F.
Roelink, Henk
author_facet Kwong, Lina
Bijlsma, Maarten F.
Roelink, Henk
author_sort Kwong, Lina
collection PubMed
description The distribution of Sonic Hedgehog (Shh) is a highly regulated and critical process for development. Several negative feedback mechanisms are in place, including the Shh-induced upregulation of Hedgehog interacting protein (Hhip). Hhip sequesters Shh, leading to a non-cell autonomous inhibition of the pathway. Hhip over-expression has a severe effect on neural tube development, raising the question why normal sites of Hhip expression have a seemingly unimpaired response to Shh. Here we show that while Hhip is able to leave its sites of synthesis to inhibit Shh non-cell autonomously, activation of Smoothened (Smo) drastically increases Hhip internalization and degradation cell autonomously. Although Hhip is unable to cell autonomously inhibit the consequences of Smo activation, it can inhibit the Shh response non-cell autonomously. Our data provide a mechanism by which the Shh ligand can activate the response and negate cell autonomous effects of Hhip, while Hhip can still induce non-cell autonomous inhibition.
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spelling pubmed-41639392015-03-12 Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signaling Kwong, Lina Bijlsma, Maarten F. Roelink, Henk Nat Commun Article The distribution of Sonic Hedgehog (Shh) is a highly regulated and critical process for development. Several negative feedback mechanisms are in place, including the Shh-induced upregulation of Hedgehog interacting protein (Hhip). Hhip sequesters Shh, leading to a non-cell autonomous inhibition of the pathway. Hhip over-expression has a severe effect on neural tube development, raising the question why normal sites of Hhip expression have a seemingly unimpaired response to Shh. Here we show that while Hhip is able to leave its sites of synthesis to inhibit Shh non-cell autonomously, activation of Smoothened (Smo) drastically increases Hhip internalization and degradation cell autonomously. Although Hhip is unable to cell autonomously inhibit the consequences of Smo activation, it can inhibit the Shh response non-cell autonomously. Our data provide a mechanism by which the Shh ligand can activate the response and negate cell autonomous effects of Hhip, while Hhip can still induce non-cell autonomous inhibition. 2014-09-12 /pmc/articles/PMC4163939/ /pubmed/25215859 http://dx.doi.org/10.1038/ncomms5849 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Kwong, Lina
Bijlsma, Maarten F.
Roelink, Henk
Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signaling
title Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signaling
title_full Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signaling
title_fullStr Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signaling
title_full_unstemmed Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signaling
title_short Shh-mediated degradation of Hhip allows cell autonomous and non-cell autonomous Shh signaling
title_sort shh-mediated degradation of hhip allows cell autonomous and non-cell autonomous shh signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163939/
https://www.ncbi.nlm.nih.gov/pubmed/25215859
http://dx.doi.org/10.1038/ncomms5849
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