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Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development

Notch signaling has been implicated in the regulation of smooth muscle differentiation, but the precise role of Notch receptors is ill defined. Although Notch3 receptor expression is high in smooth muscle, Notch3 mutant mice are viable and display only mild defects in vascular patterning and smooth...

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Detalles Bibliográficos
Autores principales: Wang, Qingqing, Zhao, Ning, Kennard, Simone, Lilly, Brenda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355134/
https://www.ncbi.nlm.nih.gov/pubmed/22615991
http://dx.doi.org/10.1371/journal.pone.0037365
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author Wang, Qingqing
Zhao, Ning
Kennard, Simone
Lilly, Brenda
author_facet Wang, Qingqing
Zhao, Ning
Kennard, Simone
Lilly, Brenda
author_sort Wang, Qingqing
collection PubMed
description Notch signaling has been implicated in the regulation of smooth muscle differentiation, but the precise role of Notch receptors is ill defined. Although Notch3 receptor expression is high in smooth muscle, Notch3 mutant mice are viable and display only mild defects in vascular patterning and smooth muscle differentiation. Notch2 is also expressed in smooth muscle and Notch2 mutant mice show cardiovascular abnormalities indicative of smooth muscle defects. Together, these findings infer that Notch2 and Notch3 act together to govern vascular development and smooth muscle differentiation. To address this hypothesis, we characterized the phenotype of mice with a combined deficiency in Notch2 and Notch3. Our results show that when Notch2 and Notch3 genes are simultaneously disrupted, mice die in utero at mid-gestation due to severe vascular abnormalities. Assembly of the vascular network occurs normally as assessed by Pecam1 expression, however smooth muscle cells surrounding the vessels are grossly deficient leading to vascular collapse. In vitro analysis show that both Notch2 and Notch3 robustly activate smooth muscle differentiation genes, and Notch3, but not Notch2 is a target of Notch signaling. These data highlight the combined actions of the Notch receptors in the regulation of vascular development, and suggest that while these receptors exhibit compensatory roles in smooth muscle, their functions are not entirely overlapping.
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spelling pubmed-33551342012-05-21 Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development Wang, Qingqing Zhao, Ning Kennard, Simone Lilly, Brenda PLoS One Research Article Notch signaling has been implicated in the regulation of smooth muscle differentiation, but the precise role of Notch receptors is ill defined. Although Notch3 receptor expression is high in smooth muscle, Notch3 mutant mice are viable and display only mild defects in vascular patterning and smooth muscle differentiation. Notch2 is also expressed in smooth muscle and Notch2 mutant mice show cardiovascular abnormalities indicative of smooth muscle defects. Together, these findings infer that Notch2 and Notch3 act together to govern vascular development and smooth muscle differentiation. To address this hypothesis, we characterized the phenotype of mice with a combined deficiency in Notch2 and Notch3. Our results show that when Notch2 and Notch3 genes are simultaneously disrupted, mice die in utero at mid-gestation due to severe vascular abnormalities. Assembly of the vascular network occurs normally as assessed by Pecam1 expression, however smooth muscle cells surrounding the vessels are grossly deficient leading to vascular collapse. In vitro analysis show that both Notch2 and Notch3 robustly activate smooth muscle differentiation genes, and Notch3, but not Notch2 is a target of Notch signaling. These data highlight the combined actions of the Notch receptors in the regulation of vascular development, and suggest that while these receptors exhibit compensatory roles in smooth muscle, their functions are not entirely overlapping. Public Library of Science 2012-05-17 /pmc/articles/PMC3355134/ /pubmed/22615991 http://dx.doi.org/10.1371/journal.pone.0037365 Text en Wang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wang, Qingqing
Zhao, Ning
Kennard, Simone
Lilly, Brenda
Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development
title Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development
title_full Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development
title_fullStr Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development
title_full_unstemmed Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development
title_short Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development
title_sort notch2 and notch3 function together to regulate vascular smooth muscle development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355134/
https://www.ncbi.nlm.nih.gov/pubmed/22615991
http://dx.doi.org/10.1371/journal.pone.0037365
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