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.
Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Matthew R
MR
Swift
Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Van N
VN
Pham
Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Daniel
D
Castranova
Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Kameha
K
Bell
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
Richard J
RJ
Poole
Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: flyingfish2@nih.gov.
Brant M
BM
Weinstein
D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D051837:COUP Transcription Factor II / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019076:Transgenes / Q000235:genetics; D014680:Veins / Q000166:cytology / Q000196:embryology; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D051837:COUP Transcription Factor II; D017931:DNA Primers; D051880:Receptors, Notch; D055760:SOXF Transcription Factors; C526281:Sox7 protein, zebrafish; D029961:Zebrafish Proteins
COUP-TFII; Cardinal vein; Dorsal aorta; Nr2f2; Zebrafish