"Riding with the Wnt": Investigating the role of Wnt signaling in cell migration

Abstract

During my PhD, my goal was to achieve a better understanding of how animals develop from embryogenesis to adulthood. Specifically, I studied how cells acquire and control their movement to sculpt the final shape of an organism. Understanding the molecular mechanisms that regulate cellular movement during development will provide insight into how these processes are deregulated in diseases such as cancer metastasis. In order to do this, I used a small nematode (round worm) called C. elegans as a model organism to study these basic molecular mechanisms. During its development, the QR neuroblast and its two descendants migrate from the posterior to the anterior part of the animal. Using time-lapse imaging I have been able to characterize the highly directional movement of these cells, visualizing the dynamic features of this cell migration process in vivo. Together with my colleagues, I found that the evolutionarily conserved Wnt signaling pathway is necessary for these cells to migrate and terminate their migration at a well-defined position along the anterior-posterior axis of the animal. Interestingly, the specific location where the cells stop is instructed by a cell intrinsic mechanism rather than extracellular guidance cues. We identified novel target genes activated by Wnt signaling that are important effectors of this cellular migration process. Beside increasing the knowledge about the shaping forces that drive animal development, the experiments performed in my PhD will be helpful to gain a deeper understanding of the molecular mechanisms that characterize cancer metastasis, and in particular the role of Wnt signaling in this process.