During the development of multi-cellular organisms, cells communicate with each other to orchestrate the complex mechanisms that lead to the formation of tissues and organs. Of particular importance is signaling through members of the highly conserved family of Wnt proteins, which are secreted, lipid modified signaling proteins that can act as short-range signaling molecules, but also as long-range morphogens that form concentration gradients to provide positional information to cells in developing tissues. A major focus of our current research is to determine how the lipid-modified Wnt protein is secreted and released from Wnt producing cells and how this process impacts on its ability to spread in the tissue. We address this question using genetic and cell biological approaches in the nematode C. elegans.
About the research
Ji, N., Middelkoop, T.C., Mentink, R.A., Betist, M.C., Tonegawa, S., Mooijman, D., Korswagen, H.C.* and van Oudenaarden, A* (2013) Feedback control of gene expression variability in the Caenorhabditis elegans Wnt pathway. Cell, 155: 869-880. *Joint senior/corresponding authors. See also: Cell video abstract
Harterink, M., Port, F., Lorenowicz, M., McGough, I., Silhankova, M., Betist, M., van Weering, J., van Heesbeen, R., Middelkoop, T., Basler, K., Cullen, P., Korswagen, H.C. (2011) A SNX3-dependent Retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion. Nature Cell Biol. 13:914-923. See also: News & Views Highlight in EMBO J
Yang, P.T., Lorenowicz, M., Silhankova, M., Coudreuse, D.Y.M., Betist, M.C., Korswagen, H.C. (2008) Wnt signaling requires retromer dependent recycling of MIG-14/Wls in Wnt producing cells. Dev. Cell, 14: 140-147.
Coudreuse, D.Y.M., Roel, G., Betist, M.C., Destree, O., Korswagen, H.C. (2006) Wnt gradient formation requires retromer function in Wnt producing cells. Science 312: 921-924.
Essers, M.A., de Vries-Smits, L.M.M., Barker, N., Polderman, P.E., Burgering, B.M.T., Korswagen, H.C. (2005) Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science 308: 1181-1184.