Focus on the retina of mice and on the tail of zebrafish

Franck Dequiedt and his colleagues in Germany were able to observe the effects of a modulation in the Notch signal via SIRT1 on the branching of the vascular system, in vitro, but also in vivo. “When we create a culture of endothelial cells on a substrate, we can see if they form a branched vascular network depending on the strength of the Notch signal”, points out Franck Dequiedt. “In vivo, we can also observe this in the development of the vascular system in thepost-natal mouse retina”, he continues. Since the pattern formed by this vascular system is very reproducible from one mouse to the next, it is easy to observe the differences caused by deregulations of the Notch signalling pathway.

 “In mice where we specifically inactivated SIRT1 in the endothelial cells, we observed a far simpler vascular network in the retina with far less branching and budding”, explains the scientist. By activating SIRT1, the researchers favoured the acetylation of the NICD and hence its stability. As a result, the intensity and duration of the Notch signal is far greater and therefore, there is a decrease in the number of tip cells ready to develop into new vascular branches...!

The same effect was observed in the development of the vascular network in the trunk of the zebrafish. “The animals we use are transparent at the start of their life and are therefore the ideal model to observe modifications in their development. When we inhibit SIRT1, the growth of the vascular network in their trunk region is reduced”, says Franck Dequiedt.  These experiments therefore confirm the action of the SIRT1 protein on the Notch signalling pathway during angiogenesis. What about the effect of the histone deacetylase in the development of other tissues under the influence of the Notch signal? “We have already observed the same regulation in the development of muscular cells”, Franck Dequiedt replies. The mechanism controlling the intensity and duration of the Notch signal by SIRT1, recently described in the journal Nature, is thus a mechanism that can be potentially applied in all tissues whose development relies on the Notch signalling pathway.