sonic hedgehog and vascular endothelial growth factor act upstream of the notch pathway during arterial endothelial differentiation

被引:678
作者
Lawson, ND [1 ]
Vogel, AM [1 ]
Weinstein, BM [1 ]
机构
[1] NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1016/S1534-5807(02)00198-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The appearance of molecular differences between arterial and venous endothelial cells before circulation suggests that genetic factors determine these cell types. We find that vascular endothelial growth factor (vegf) acts downstream of sonic hedgehog (shh) and upstream of the Notch pathway to determine arterial cell fate. Loss of Vegf or Shh results in loss of arterial identity, while exogenous expression of these factors causes ectopic expression of arterial markers. Microinjection of vegf mRNA into embryos lacking Shh activity can rescue arterial differentiation. Finally, activation of the Notch pathway in the absence of Vegf signaling can rescue arterial marker gene expression. These studies reveal a complex signaling cascade responsible for establishing arterial cell fate and suggest differential effects of Vegf on developing endothelial cells.
引用
收藏
页码:127 / 136
页数:10
相关论文
共 52 条
[1]   Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis [J].
Adams, RH ;
Wilkinson, GA ;
Weiss, C ;
Diella, F ;
Gale, NW ;
Deutsch, U ;
Risau, W ;
Klein, R .
GENES & DEVELOPMENT, 1999, 13 (03) :295-306
[2]   Delta-mediated specification of midline cell fates in zebrafish embryos [J].
Appel, B ;
Fritz, A ;
Westerfield, M ;
Grunwald, DJ ;
Eisen, JS ;
Riley, BB .
CURRENT BIOLOGY, 1999, 9 (05) :247-256
[3]   Insights into early vasculogenesis revealed by expression of the ETS-domain transcription factor Fli-1 in wild-type and mutant zebrafish embryos [J].
Brown, LA ;
Rodaway, ARF ;
Schilling, TF ;
Jowett, T ;
Ingham, PW ;
Patient, RK ;
Sharrocks, AD .
MECHANISMS OF DEVELOPMENT, 2000, 90 (02) :237-252
[4]  
Chen JN, 1996, DEVELOPMENT, V123, P293
[5]  
Cleaver O, 2000, DEVELOPMENT, V127, P869
[6]   Teratogen-mediated inhibition of target tissue response to Shh signaling [J].
Cooper, MK ;
Porter, JA ;
Young, KE ;
Beachy, PA .
SCIENCE, 1998, 280 (5369) :1603-1607
[7]  
Eriksson J, 2000, J MORPHOL, V244, P167, DOI 10.1002/(SICI)1097-4687(200006)244:3<167::AID-JMOR2>3.3.CO
[8]  
2-A
[9]  
Ferrara N, 1999, CURR TOP MICROBIOL, V237, P1
[10]   Ephrin-B2 selectively marks arterial vessels and neovascularization sites in the adult, with expression in both endothelial and smooth-muscle cells [J].
Gale, NW ;
Baluk, P ;
Pan, L ;
Kwan, M ;
Holash, J ;
DeChiara, TM ;
McDonald, DM ;
Yancopoulos, GD .
DEVELOPMENTAL BIOLOGY, 2001, 230 (02) :151-160