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Notch signaling in early embryonic vascular differentiation
Author(s) -
Vivian Jay,
Copeland Jessica
Publication year - 2008
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.22.1_supplement.522.2
Subject(s) - notch signaling pathway , hes3 signaling axis , microbiology and biotechnology , biology , signal transduction , embryonic stem cell , notch proteins , cellular differentiation , yolk sac , phenotype , transgene , tgf beta signaling pathway , function (biology) , transforming growth factor , embryo , genetics , gene
The signaling cascades that direct the morphological differentiation of the vascular system during early embryogenesis are not well defined. Several signaling pathways, including the Notch and VEGF signaling, are critical for the formation of the vasculature in the mouse. To further understand the role of Notch signaling during endothelial differentiation, we are using a both loss‐of‐function and gain‐of‐function approaches in vivo. Embryos with activated Notch signaling in the vasculature display a variety of defects, and do survive not after E10.5. Most notably, the extraembryonic vasculature of the yolk sac displays remodeling differentiation defects, with few matured vessels. These phenotypes are distinct from tissue specific loss‐of‐function of Rbpj, a transcriptional regulator of Notch activity. Gene expression analysis indicated aberrant expression in a variety of genes in these models. In particular, VEGF and TGF‐beta family members show coordinate expression defects in the loss‐of‐function and gain‐of‐function models. This data suggests potential regulatory connections between Notch signaling and other signaling pathways during endothelial differentiation. Based on these findings, we are exploring other transgenic and embryo culture models to further understand the relevance of the of VEGF‐ and TGF‐beta‐related signaling during Notch‐mediated endothelial differentiation.