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Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia

The primary cilia play essential roles in Hh-dependent Gli2 activation and Gli3 proteolytic processing in mammals. However, the roles of the cilia in Gli1 activation remain unresolved due to the loss of Gli1 transcription in cilia mutant embryos, and the inability to address this question by overexp...

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Autores principales: Wang, Yuan, Zeng, Huiqing, Liu, Aimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473256/
https://www.ncbi.nlm.nih.gov/pubmed/30791390
http://dx.doi.org/10.3390/jdb7010005
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author Wang, Yuan
Zeng, Huiqing
Liu, Aimin
author_facet Wang, Yuan
Zeng, Huiqing
Liu, Aimin
author_sort Wang, Yuan
collection PubMed
description The primary cilia play essential roles in Hh-dependent Gli2 activation and Gli3 proteolytic processing in mammals. However, the roles of the cilia in Gli1 activation remain unresolved due to the loss of Gli1 transcription in cilia mutant embryos, and the inability to address this question by overexpression in cultured cells. Here, we address the roles of the cilia in Gli1 activation by expressing Gli1 from the Gli2 locus in mouse embryos. We find that the maximal activation of Gli1 depends on the cilia, but partial activation of Gli1 by Smo-mediated Hh signaling exists in the absence of the cilia. Combined with reduced Gli3 repressors, this partial activation of Gli1 leads to dorsal expansion of V3 interneuron and motor neuron domains in the absence of the cilia. Moreover, expressing Gli1 from the Gli2 locus in the presence of reduced Sufu has no recognizable impact on neural tube patterning, suggesting an imbalance between the dosages of Gli and Sufu does not explain the extra Gli1 activity. Finally, a non-ciliary Gli2 variant present at a higher level than Gli1 when expressed from the Gli2 locus fails to activate Hh pathway ectopically in the absence of the cilia, suggesting that increased protein level is unlikely the major factor underlying the ectopic activation of Hh signaling by Gli1 in the absence of the cilia.
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spelling pubmed-64732562019-04-29 Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia Wang, Yuan Zeng, Huiqing Liu, Aimin J Dev Biol Article The primary cilia play essential roles in Hh-dependent Gli2 activation and Gli3 proteolytic processing in mammals. However, the roles of the cilia in Gli1 activation remain unresolved due to the loss of Gli1 transcription in cilia mutant embryos, and the inability to address this question by overexpression in cultured cells. Here, we address the roles of the cilia in Gli1 activation by expressing Gli1 from the Gli2 locus in mouse embryos. We find that the maximal activation of Gli1 depends on the cilia, but partial activation of Gli1 by Smo-mediated Hh signaling exists in the absence of the cilia. Combined with reduced Gli3 repressors, this partial activation of Gli1 leads to dorsal expansion of V3 interneuron and motor neuron domains in the absence of the cilia. Moreover, expressing Gli1 from the Gli2 locus in the presence of reduced Sufu has no recognizable impact on neural tube patterning, suggesting an imbalance between the dosages of Gli and Sufu does not explain the extra Gli1 activity. Finally, a non-ciliary Gli2 variant present at a higher level than Gli1 when expressed from the Gli2 locus fails to activate Hh pathway ectopically in the absence of the cilia, suggesting that increased protein level is unlikely the major factor underlying the ectopic activation of Hh signaling by Gli1 in the absence of the cilia. MDPI 2019-02-19 /pmc/articles/PMC6473256/ /pubmed/30791390 http://dx.doi.org/10.3390/jdb7010005 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Yuan
Zeng, Huiqing
Liu, Aimin
Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia
title Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia
title_full Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia
title_fullStr Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia
title_full_unstemmed Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia
title_short Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia
title_sort distinct activities of gli1 and gli2 in the absence of ift88 and the primary cilia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473256/
https://www.ncbi.nlm.nih.gov/pubmed/30791390
http://dx.doi.org/10.3390/jdb7010005
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