Table 1.
Semaphorin ligand mutants with cardiovascular defects
| Mutation(s) | Receptors or Ligands | Stage of lethality | Cardiovascular phenotypes and functions | Refs. |
|---|---|---|---|---|
| Semaphorins | ||||
| Sema3a −/− | Plexin A1-A4, D1, Nrp1-2, Vegfr2 | Postnatal | Atrial defects, sinus bradycardia, lymphatic valve defects, vascular patterning defects. Sema3a inhibits angiogenesis. | (Bouvree et al., 2012; Chen et al., 2013; Ieda et al., 2007; Jurisic et al., 2012) |
| Sema3b −/− | Plexin A1-A4, Nrp1-2, Vegfr2 | Viable | No obvious cardiac defects. Sema3b inhibits angiogenesis. | (Falk et al., 2005) |
| Sema3c −/− | Plexin A2, D1, Nrp1-2 | Postnatal (varies with strain) | PTA, VSD, aortic arch defects. Sema3c promotes angiogenesis. | (Feiner et al., 2001) |
| Sema3d −/− | Nrp1 | Viable | Anomalous pulmonary venous connection, ASD. Sema3d repels pulmonary vein endothelial cells. | (Degenhardt et al., 2013a; Katz et al., 2012) |
| Sema3e −/− | Plexin As (neuropilin dependent), Plexin D1 | Viable | Vascular patterning defects. Sema3e restricts blood vessel growth to the intersomitic boundaries. Inhibits angiogenesis. A 61-kDa Sema3e isoform promotes endothelial cell migration. | (Casazza et al., 2010; Gu et al., 2005) |
| Sema3f −/− | Plexin A3, A4, Nrp1-2 | Viable | No obvious phenotype. Sema3f inhibits angiogenesis and lymphangiogenesis. | (Sahay et al., 2003) |
| Sema3g −/− | Nrp1-2 | Viable | Vascular remodeling defects. Sema3g promote angiogenesis. | (Kutschera et al., 2011) |
| Sema4a −/− | Plexin B1-3, Plexin D1, Met, Erbb2 | Viable | Enhanced angiogenesis in response to Vegf or inflammatory stimuli. Sema4a inhibits angiogenesis. | (Kumanogoh et al., 2005; Toyofuku et al., 2007) |
| Sema4d −/− | Plexin B1-2, C1, Met, Erbb2 | Viable | Delayed atherosclerotic plaque formation due to impaired neovascularization. Sema4d promotes angiogenesis. | (Yukawa et al., 2010; Zhu et al., 2009) |
| Sema5a −/− | Plexin A3, B3, Nrp2, Met, Erbb2 | Viable or embryonic | Defective cranial blood vessel remodeling. Sema5a promotes angiogenesis. | (Fiore et al., 2005; Matsuoka et al., 2011) |
| Sema6a −/− | Plexin A1, A2, A4, Vegfr2 | Viable | Abnormal retinal vascular development. Sema6a promotes angiogenesis. A soluble form of Sema6a inhibits angiogenesis. | (Segarra et al., 2012) |
| Sema6d −/− | Plexin A1 | Viable | No obvious phenotype in mice. Sema6d modulates compact layer expansion and trabeculation in chick. | (Takamatsu et al., 2010; Toyofuku et al., 2004a; Toyofuku et al., 2004 b) |
VSD, ventricular septal defect; PTA, persistent truncus arteriosus; ASD, atrial septal defect.