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During development, the mammalian circulatory system is fixed in place before blood-flow commences. Different sets of genes control artery and vein formation, long before the vessels can be distinguished on the basis of direction of blood flow. This understanding has been mainly due to the discovery that vascular endothelial growth factor (Vegf) is necessary for arterial development.
Now, in the June 1 issue of Genes & Development, Nathan D. Lawson and colleagues at the National Institutes of Health demonstrate that the signaling molecule phospholipase C gamma-1 (plcg1) also plays an important part in artery formation (Genes & Development 17:1346-1351, June 1, 2003).
Lawson et al. used transgenic zebrafish with fluorescent blood vessels to search for new genes involved in artery development. They found that a mutation in one gene, plcg1, inhibited formation of arteries but not veins. In addition, the plcg1 mutant did not express several artery-specific genes, a result consistent with the known role of plcg1 as a signaling molecule.
The similar phenotype of plcg1 and Vegf mutants suggested these two genes might act in the same pathway. To test this, the authors injected Vegf mRNA into plcg1 mutant and wildtype embryos and assayed the levels of artery-specific genes. For these genes to be induced at high levels, plcg1 had to be present in the embryos, suggesting that plcg1 acts downstream of Vegf.
The discovery of the involvement of plcg1 in arterial development further confirms the importance of the Vegf pathway in the process. Mutations in genes in the same pathway in humans could cause congenital defects in the circulatory system.
References
| 1. | | N.D. Lawson et al., "Sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation," Developmental Cell, 3:127-136, July 2002.
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| 2. | | Y.S. Mukouyama et al., "Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin," Cell, 109: 693-705, 2002.
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| 3. | | [http://www.genesdev.org/cgi/content/abstract/17/11/1346?etoc]
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| | | N.D. Lawson et al., "Phospholipase C gamma-1 is required downstream of vascular endothelial growth factor during arterial development," Genes & Development, 17:1346-1351, 2003.
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| 4. | | [http://www.nih.gov/]
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| | | National Institutes of Health
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