Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biophysics, COUP-TFII, Endothelial specification, (Lymph)angiogenesis, Zebrafish, Xenopus laevis, Prox1, ENDOTHELIAL-CELLS, LYMPHANGIOGENESIS, VASCULATURE, PROX1, SPECIFICATION, EXPRESSION, UPSTREAM, NOTCH, SOX18, Animals, COUP Transcription Factor II, Cardiovascular Abnormalities, Cell Movement, Endothelium, Vascular, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Homeodomain Proteins, Lymphangiogenesis, Tumor Suppressor Proteins, Veins, KUL-CoE-Cardio, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1101 Medical Biochemistry and Metabolomics, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry

Abstract:

Transcription factors play a central role in cell fate determination. Gene targeting in mice revealed that Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII, also known as Nuclear Receptor 2F2 or NR2F2) induces a venous phenotype in endothelial cells (ECs). More recently, NR2F2 was shown to be required for initiating the expression of Prox1, responsible for lymphatic commitment of venous ECs. Small animal models like zebrafish embryos and Xenopus laevis tadpoles have been very useful to elucidate mechanisms of (lymph) vascular development. Therefore, the role of NR2F2 in (lymph) vascular development was studied by eliminating its expression in these models. Like in mice, absence of NR2F2 in zebrafish resulted in distinct vascular defects including loss of venous marker expression, major trunk vessel fusion and vascular leakage. Both in zebrafish and Xenopus the development of the main lymphatic structures was severely hampered. NR2F2 knockdown significantly decreased prox1 expression in zebrafish ECs and the same manipulation affected lymphatic (L)EC commitment, migration and function in Xenopus tadpoles. Therefore, the role of NR2F2 in EC fate determination is evolutionary conserved.