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Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila
Planar cell polarity (PCP) and neural tube defects (NTDs) are linked, with a subset of NTD patients found to harbor mutations in PCP genes, but there is limited data on whether these mutations disrupt PCP signaling in vivo. The core PCP gene Van Gogh (Vang), Vangl1/2 in mammals, is the most specific...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180057/ https://www.ncbi.nlm.nih.gov/pubmed/32234212 http://dx.doi.org/10.7554/eLife.53532 |
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author | Humphries, Ashley C Narang, Sonali Mlodzik, Marek |
author_facet | Humphries, Ashley C Narang, Sonali Mlodzik, Marek |
author_sort | Humphries, Ashley C |
collection | PubMed |
description | Planar cell polarity (PCP) and neural tube defects (NTDs) are linked, with a subset of NTD patients found to harbor mutations in PCP genes, but there is limited data on whether these mutations disrupt PCP signaling in vivo. The core PCP gene Van Gogh (Vang), Vangl1/2 in mammals, is the most specific for PCP. We thus addressed potential causality of NTD-associated Vangl1/2 mutations, from either mouse or human patients, in Drosophila allowing intricate analysis of the PCP pathway. Introducing the respective mammalian mutations into Drosophila Vang revealed defective phenotypic and functional behaviors, with changes to Vang localization, post-translational modification, and mechanistic function, such as its ability to interact with PCP effectors. Our findings provide mechanistic insight into how different mammalian mutations contribute to developmental disorders and strengthen the link between PCP and NTD. Importantly, analyses of the human mutations revealed that each is a causative factor for the associated NTD. |
format | Online Article Text |
id | pubmed-7180057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-71800572020-04-27 Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila Humphries, Ashley C Narang, Sonali Mlodzik, Marek eLife Developmental Biology Planar cell polarity (PCP) and neural tube defects (NTDs) are linked, with a subset of NTD patients found to harbor mutations in PCP genes, but there is limited data on whether these mutations disrupt PCP signaling in vivo. The core PCP gene Van Gogh (Vang), Vangl1/2 in mammals, is the most specific for PCP. We thus addressed potential causality of NTD-associated Vangl1/2 mutations, from either mouse or human patients, in Drosophila allowing intricate analysis of the PCP pathway. Introducing the respective mammalian mutations into Drosophila Vang revealed defective phenotypic and functional behaviors, with changes to Vang localization, post-translational modification, and mechanistic function, such as its ability to interact with PCP effectors. Our findings provide mechanistic insight into how different mammalian mutations contribute to developmental disorders and strengthen the link between PCP and NTD. Importantly, analyses of the human mutations revealed that each is a causative factor for the associated NTD. eLife Sciences Publications, Ltd 2020-04-01 /pmc/articles/PMC7180057/ /pubmed/32234212 http://dx.doi.org/10.7554/eLife.53532 Text en © 2020, Humphries et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Humphries, Ashley C Narang, Sonali Mlodzik, Marek Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila |
title | Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila |
title_full | Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila |
title_fullStr | Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila |
title_full_unstemmed | Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila |
title_short | Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila |
title_sort | mutations associated with human neural tube defects display disrupted planar cell polarity in drosophila |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180057/ https://www.ncbi.nlm.nih.gov/pubmed/32234212 http://dx.doi.org/10.7554/eLife.53532 |
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