title: Transcription factor COUP-TFII is indispensable for venous and lymphatic development in zebrafish and Xenopus laevis.
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.
authors.affiliation: Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs & Navorsing 1, Herestraat 49, B-3000 Leuven, Belgium. xabier.lopezaranguren@med.kuleuven.be
authors.forename: Xabier L
authors.initials: XL
authors.lastname: Aranguren
authors.forename: Manu
authors.initials: M
authors.lastname: Beerens
authors.forename: Wouter
authors.initials: W
authors.lastname: Vandevelde
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
mesh_terms: D000818:Animals; D051837:COUP Transcription Factor II / Q000235:genetics / Q000502:physiology*; D018376:Cardiovascular Abnormalities / Q000235:genetics; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics; D042583:Lymphangiogenesis / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014680:Veins / Q000196:embryology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D051837:COUP Transcription Factor II; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein