The main thing about reaching a ripe old age seems to be about cracking the nut of those diseases affecting organ systems deriving substantially or exclusively from mesodermal cells, such as heart, vascular system, blood, kidneys, skeleton and musculature. This is why the “Cells into Organs” network of excellence, which includes 24 groups in 12 universities across Europe, has been focusing on an integrated approach to mesodermally-derived organ systems, bringing together developmental genetics and experimental embryology with modern cell biology and genome scale analysis.
Professors Walter Gehring and Markus Affolter’s groups work at the Biozentrum of Basel University in Switzerland. Professor Gehring, who found the crucial Pax-6 gene responsible for eye development, has been looking for a cure of macular eye degeneration, whereas Professor Affolter is in charge of a zebrafish embryo study researching angiogenesis, which means the recruitment of new blood vessels as a normal process in growth and development, but also as an essential component of tumours’ metastatic pathway.
The main implication is that these vessels provide the main route by which tumour cells exit the main tumour site and enter the bloodstream. A highly vascularized tumour has indeed a higher chance to metastasize.
Zebrafish looks like one of the most promising animal systems in the study of angiogenesis just now. The formation of intersegmental blood vessels (ISVs) in the zebrafish embryo serves as a paradigm to study angiogenesis in vivo. The vascular lumen is then established via formation of vacuoles, which eventually fuse with those of adjacent endothelial cells to generate a seamless tube with an intracellular lumen.
To investigate the cellular architecture and the development of ISVs in detail, Professor Affolter’s team have analysed the arrangement of endothelial cell junctions and have performed single cell live imaging. They found out that, surprisingly, endothelial cells are not arranged in a linear head-to-tail configuration but overlap extensively and form a multicellular tube, which contains an extracellular lumen.
Their findings show that a number of cellular behaviours, such as cell divisions, cell rearrangements and dynamic alterations in the contacts between cells have to be considered in vivo. “It’s normally very difficult to study vessel development in an organism as it happens”, Professor Affolter says . “But with zebrafish, which develops very quickly, we can study the lumen while it’s forming in each vessel. And our work has changed the way we think about it. Literature says that endothelial cells in vitro align and luminize by hollowing out, so a hollow cell would follow a hollow cell in a row, and so on. But when we looked at the cells in vivo, we noticed that this is not the case. We saw instead that the lumen develops between cells as they grow out”.
The underlying mistery, Professor Affolter adds, still concerns “how these tubes are joined. This is what we want to study now”.
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