Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development

Hdl Handle:
http://hdl.handle.net/10675.2/711
Title:
Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development
Authors:
Wang, Qingqing; Zhao, Ning; Kennard, Simone; Lilly, Brenda
Abstract:
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.
Citation:
PLoS One. 2012 May 17; 7(5):e37365
Issue Date:
17-May-2012
URI:
http://hdl.handle.net/10675.2/711
DOI:
10.1371/journal.pone.0037365
PubMed ID:
22615991
PubMed Central ID:
PMC3355134
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Vascular Biology Center: Faculty Research and Publication

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Qingqingen_US
dc.contributor.authorZhao, Ningen_US
dc.contributor.authorKennard, Simoneen_US
dc.contributor.authorLilly, Brendaen_US
dc.date.accessioned2012-10-26T16:40:50Z-
dc.date.available2012-10-26T16:40:50Z-
dc.date.issued2012-05-17en_US
dc.identifier.citationPLoS One. 2012 May 17; 7(5):e37365en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22615991en_US
dc.identifier.doi10.1371/journal.pone.0037365en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/711-
dc.description.abstractNotch 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.en_US
dc.rightsWang et al. 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 credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectMusculoskeletal Systemen_US
dc.subjectMuscleen_US
dc.subjectMuscle Typesen_US
dc.subjectDevelopmental Biologyen_US
dc.subjectMolecular Developmenten_US
dc.subjectSignalingen_US
dc.subjectCell Differentiationen_US
dc.subjectGeneticsen_US
dc.subjectGenetic Mutationen_US
dc.subjectMedicineen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectMusculoskeletal Systemen_US
dc.subjectMuscleen_US
dc.subjectMuscle Typesen_US
dc.subjectCardiovascularen_US
dc.subjectVascular Biologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Differentiationen_US
dc.subject.meshCell Lineen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshMiceen_US
dc.subject.meshMuscle, Smooth, Vascularen_US
dc.subject.meshPregnancyen_US
dc.subject.meshReceptor, Notch2en_US
dc.subject.meshReceptors, Notchen_US
dc.subject.meshYolk Sacen_US
dc.titleNotch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Developmenten_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3355134en_US
dc.contributor.corporatenameVascular Biology Center-
All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.