Table 1.
Factors involved in regulating arterial, venous and lymphatic cell fates
| Factor | Phenotype/Role | References |
|---|---|---|
| Arterial identity | ||
| Shh | Loss of Shh results in lack of arterial identity in zebrafish. Shh acts upstream of VEGF. | Lawson et al., 2002 |
| VEGF | VEGF acts downstream of Shh signaling to activate Notch via the PLCγ/ERK pathway in zebrafish. Mutant mice expressing only VEGF188 lack arterial differentiation. |
Lawson et al., 2002; Stalmans et al., 2002 Hong et al., 2006; Covassin et al., 2009 |
| Nrp1 | Null mice display impaired arterial differentiation. Nrp1 is involved in a positive feedback loop of VEGF signaling. |
Jones et al., 2008; Mukouyama et al., 2005 |
| Notch | Notch acts downstream of Shh and VEGF signaling in zebrafish. Notch1; Notch4 mutant mice have abnormal vascular development. |
Lawson et al., 2001; Lawson et al., 2002 Krebs et al., 2000 |
| Dll4 | Null mice lack arterial specification. |
Duarte et al., 2004; Gale et al., 2004; Krebs et al., 2004 |
| Dll1 | Null mice fail to maintain arterial identity. | Sorensen et al., 2009 |
| Hey1/2 (Grl) |
Null mice lack arterial specification. Lack of grl in zebrafish results in loss of arterial specification. |
Zhong et al., 2001; Fisher et al., 2004 Kokubo et al., 2005 |
| Foxc1/c2 | Foxc1; Foxc2 mutant mice lack arterial specification. Foxc1 and Foxc2 directly regulate Dll4 and Hey2 expression. Foxc1 and Foxc2 are also involved in lymphatic vessel development. |
Kume et al., 2001; Seo et al., 2006 Hayashi and Kume, 2008 |
| Sox7/18 | Lack of Sox7/18 results in loss of arterial identity in zebrafish. |
Cermenati et al., 2008; Herpers et al., 2008 Pendeville et al., 2008 |
| Snrk-1 | Snrk-1 acts downstream or parallel to Notch signaling in zebrafish. | Chun et al., 2009 |
| Dep1 | Dep1 acts upstream of PI3K in arterial specification in zebrafish. | Rodriguez et al., 2008 |
| Crlr | Shh regulates VEGF activity by controlling crlr expression in zebrafish. | Nicoli et al., 2008 |
| EphrinB2 | Null mice lack boundaries between arteries and veins. EphrinB2 is involved in lymphatic vascular remodeling and maturation. |
Wang et al., 1998; Adams et al., 1999; Gerety and Anderson, 2002; Makinen et al., 2005 |
| Venous identity | ||
| COUP-TFII | COUP-TFII suppresses arterial cell fate by inhibiting Nrp1 and Notch. COUP-TFII also interacts with Prox1 to regulate lymphatic gene expression. |
You et al., 2005; Lee et al., 2009 Yamazaki et al., 2009 |
| EphB4 | Null mice lack boundaries between arteries and veins. | Gerety et al., 1999 |
| Lymphatic identity | ||
| Sox18 | Null mice fail to specify lymphatic endothelial cells. Sox18 induces Prox1 expression. | Francois et al., 2008 |
| Prox1 | Prox1 induces lymphatic markers and maintains lymphatic cell identity. |
Wigle and Oliver, 1999; Wigle et al., 2002 Hong et al., 2002; Petrova et al., 2002 Johnson et al., 2008 |