23 August 2011 00:00 hrs.
Wnts on the move: mechanisms of Wnt secretion and Wnt dependent cell migration.

Dr. Rik Korswagen, Hubrecht Institute, Utrecht

23-08-2011 00:00:00Europe/AmsterdamWnts on the move: mechanisms of Wnt secretion and Wnt dependent cell migration.

Remarks / more information:

Rik-KorswagenDuring the development of complex 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. In addition, Wnt proteins are important regulators of adult stem cells and deregulation of Wnt signaling is one of the major causes of cancer. Advancing our understanding of the Wnt signaling mechanism is therefore essential for the development of future cancer treatments. In the past decade, much attention has been focused on how binding of Wnt to its receptors triggers the expression of specific target genes and we now have a detailed understanding of the so-called canonical Wnt/beta-catenin signaling pathway that is involved. Wnt proteins also activate other signaling pathways and especially the signaling mechanisms that control Wnt dependent cell migration are still mostly unexplored. Also, it is still largely unknown how the lipid-modified Wnt protein is secreted from producing cells and how the range of Wnt signaling in the tissue is controlled. My group addresses these questions using genetic and cell biological approaches in the nematode C. elegans, where we combine genetic screens with detailed functional analysis to identify new signaling mechanisms. Our ultimate aim is to translate these results to the mammalian system, using approaches in tissue-culture cells and more recently by generating conditional mouse models. I will talk about our work on the mechanism of Wnt secretion, discussing our recent findings on the function of the novel SNX3 retromer pathway in this process. Time permitting, I will also talk about how we use a new single molecule mRNA FISH method in C. elegans to quantitatively determine gene expression in vivo, revealing important new insight into how cells are instructed to respond through different Wnt signaling mechanisms.

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