A cell biologist’s most valuable asset is his or her toolbox…the collection of techniques and methods they can use to ask a question about a cell. For example, to figure out how important a given protein is in a specific process, there are many options…good old fashioned deletion or mutation of its gene, chemical inhibition, imaging its localization, finding binding partners, etc. Varying results from each of these approaches can lead to confusion, but a good scientist can turn that confusion into a more fully developed understanding.
Angiogenesis is the formation of blood vessels off of existing vessels, and is a key process in development and tumorigenesis. VEGF (vascular endothelial growth factor) is a potent activator of angiogenesis, and Notch is a protein that converts endothelial cells into tip and stalk cells, which are cell types required for vessel formation. A research group found that function-blocking antibodies for VEGFR-3, a VEGF receptor protein, caused a decrease in angiogenesis in developing mice and in tumors. However, this same research group more recently found that complete deletion of the VEGFR-3 gene caused excessive branching and sprouting during angiogenesis, as well as decreased Notch signaling. By finding varying results with similar, but subtly different approaches, Tammela and colleagues were able to distinguish bimodal functions of VEGFR-3 during angiogenesis. In the images above, blood vessels lacking the gene for VEGFR-3 (left) have more branching than wild-type vessels (right). Vessels lacking VEGFR-3 also have more filopodia (yellow dots, bottom row), actin-rich protrusions used by tip cells to guide branching.
Tammela, T., Zarkada, G., Nurmi, H., Jakobsson, L., Heinolainen, K., Tvorogov, D., Zheng, W., Franco, C., Murtomäki, A., Aranda, E., Miura, N., Ylä-Herttuala, S., Fruttiger, M., Mäkinen, T., Eichmann, A., Pollard, J., Gerhardt, H., & Alitalo, K. (2011). VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling Nature Cell Biology, 13 (10), 1202-1213 DOI: 10.1038/ncb2331
Adapted by permission from Macmillan Publishers Ltd, copyright ©2011