Transcription factor COUP-TFII is indispensable for venous and lymphatic development in zebrafish and Xenopus laevis.

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.

Aranguren XL ，Beerens M ，Vandevelde W ，Dewerchin M ，Carmeliet P ，Luttun A ... -  《-》

Divergence of zebrafish and mouse lymphatic cell fate specification pathways.

van Impel A ，Zhao Z ，Hermkens DM ，Roukens MG ，Fischer JC ，Peterson-Maduro J ，Duckers H ，Ober EA ，Ingham PW ，Schulte-Merker S ... -  《-》

COUP-TFII orchestrates venous and lymphatic endothelial identity by homo- or hetero-dimerisation with PROX1.

Aranguren XL ，Beerens M ，Coppiello G ，Wiese C ，Vandersmissen I ，Lo Nigro A ，Verfaillie CM ，Gessler M ，Luttun A ... -  《-》

SoxF factors and Notch regulate nr2f2 gene expression during venous differentiation in zebrafish.

Initial embryonic determination of artery or vein identity is regulated by genetic factors that work in concert to specify the endothelial cell׳s (EC) fate, giving rise to two structurally unique components of the circulatory loop. The Shh/VEGF/Notch pathway is critical for arterial specification, while the orphan receptor nr2f2 (COUP-TFII) has been implicated in venous specification. Studies in mice have shown that nr2f2 is expressed in venous but not arterial ECs, and that it preferentially induces markers of venous cell fate. We have examined the role of nr2f2 during early arterial-venous development in the zebrafish trunk. We show that expression of a subset of markers of venous endothelial identity requires nr2f2, while the expression of nr2f2 itself requires sox7 and sox18 gene function. However, while sox7 and sox18 are expressed in both the cardinal vein and the dorsal aorta during early trunk development, nr2f2 is expressed only in the cardinal vein. We show that Notch signaling activity present in the dorsal aorta suppresses expression of nr2f2, restricting nr2f2-dependent promotion of venous differentiation to the cardinal vein.

Swift MR ，Pham VN ，Castranova D ，Bell K ，Poole RJ ，Weinstein BM ... -  《-》

Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development.

Lin FJ ，Chen X ，Qin J ，Hong YK ，Tsai MJ ，Tsai SY ... -  《-》