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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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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. |
format | Online Article Text |
id | pubmed-4163939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
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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