Abstract:
:Endothelial to mesenchymal transition (EMT) that occurs during cardiac outflow tract (OFT) development is critical for formation of the semilunar valves. Fibulin-1 (Fbln1) is an extracellular matrix protein that is present at several sites of EMT, including the OFT (i.e., E9.5-10.5). The aim of this study was to determine the role of Fbln1 in EMT during the earliest events of OFT development. Examination of proximal OFT cushions in Fbln1 null embryos detected hypercellularity at both E9.5 (93% increase; p = 0.002) and E10.5 (43% increase; p = 0.01) as compared to wild type, suggesting that Fbln1 normally suppresses OFT endocardial cushion EMT. This was supported by studies of proximal OFT cushion explants, which showed that explants from Fbln1 null embryos displayed a 58% increase in cells migrating from the explants as compared to wild type (p = 0.005). We next evaluated the effects of Fbln1 deficiency on the expression of factors that regulate proximal OFT EMT. At E9.5, Fbln1 null proximal OFT endocardium and EMT-derived mesenchyme showed increased TGFβ2 (58% increase; p = 0.01) and increased Snail1-positive nuclei (27% increase; p = 0.0003). Histological examination of OFT cushions in Fbln1 null embryos (E9.5) also detected cells present in the cushion that were determined to be erythrocytes based on round morphology, autofluorescence, and positive staining for hemoglobin. Erythrocytes were also detected in Fbln1 null OFT cushions at E10.5. Together, the findings indicate that Fbln1 normally suppresses proximal OFT EMT preventing proximal cushion hypercellularity and blood cell accumulation.
journal_name
Mech Devjournal_title
Mechanisms of developmentauthors
Harikrishnan K,Cooley MA,Sugi Y,Barth JL,Rasmussen LM,Kern CB,Argraves KM,Argraves WSdoi
10.1016/j.mod.2014.12.005subject
Has Abstractpub_date
2015-05-01 00:00:00pages
123-32eissn
0925-4773issn
1872-6356pii
S0925-4773(14)00091-4journal_volume
136pub_type
杂志文章abstract::Dickkopf-1 (dkk-1) is member of a novel family of secreted proteins and functions in head induction during Xenopus embryogenesis, acting as a potent inhibitor of Wnt signalling. Here we report: (1) the isolation of two additional murine members of the dkk family, dkk-2 and dkk-3; and (2) analysis of adult and embryoni...
journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
pub_type: 杂志文章
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journal_title:Mechanisms of development
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更新日期:2004-07-01 00:00:00
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journal_title:Mechanisms of development
pub_type: 杂志文章
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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