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Temporal and functional study of TGFβ regulated genes during chicken AV canal formation
Author(s) -
Tavares Andre Luiz Pasqua,
Runyan Raymond Bruce
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.302.2
Subject(s) - brachyury , downregulation and upregulation , epithelial–mesenchymal transition , mesenchyme , microbiology and biotechnology , transforming growth factor , transcription factor , runx2 , noggin , transforming growth factor beta , chemistry , biology , cancer research , bone morphogenetic protein , mesoderm , embryonic stem cell , mesenchymal stem cell , gene , biochemistry
In the atrioventricular canal (AVC) of the embryonic heart, endothelia undergo an epithelial‐mesenchymal transition (EMT). This EMT is a multi‐step event, wherein TGFß2 mediates activation while TGFß3 mediates cell invasion. BMP2 has an unclear role in this EMT. We examined in vivo and in vitro patterns of expression of EMT‐related genes. In the chick, EMT is seen at stage 17 although signaling processes begin at stage 14. Our objective is to identify critical transcription factor function during EMT. We examined mRNA for Sox8, Sox11, Sip1, Brachyury, Hey2 and Runx2 by qPCR. Starting at stage 14, Sox8 and Hey2 showed upregulation while Brachyury was downregulated. Sip1 and Runx2 were down‐regulated only after EMT was visible. Sox11 mRNA levels did not show significant change (stages 14‐20). We explored changes in expression after TGFβ2, TGFβ3 or BMP inhibition of AVC explants on collagen gels. Anti‐TGFβ2 treatment produced significant upregulation of Sox8 and down‐regulation of Sox11, Sip1 and Runx2 while anti‐TGFβ3 treatment caused significant down‐regulation of Sox8, Sip1 and Runx2. Noggin treatment caused significant upregulation of Sox8, Sox11, Sip1 and Hey2 and down‐regulation of Brachyury. Localization of these molecules showed they were present in AVC endothelium and mesenchyme at the analyzed stages. These data suggest that each of these transcription factors may play a role in cardiac EMT. NHLBI.Grant Funding Source NHLBI