Developing and analysing novel tools to study endogenous WNT signalling in mice

Developmental biology addresses one of the most beautiful miracles of life: how just one little cell can turn into an entire organism, built out of billions of cells. To answer the fundamental question of how this happens, it is essential to visualize cells, tissues and organs – allowing us to follow them during the process of tissue morphogenesis. In this day and age, scientists are also increasingly interested in understanding what goes on inside each of these cells, since cell behaviour is ultimately organised at the molecular level through specific gene expression and protein activity patterns. Knowing how an organism is built is not only interesting, but also essential to intervene when these processes go wrong, for example when developmental defects or uncontrolled cell growth occur.
Cells are tightly controlled by the actions of several signal transduction pathways that maintain an intricate balance of cell proliferation, differentiation and survival. The WNT signalling pathway is essential in these processes, driving both embryonic development and tissue homeostasis throughout the multicellular animal kingdom. When Wnt signalling goes awry, this can result in a range of diseases, including cancer. Over forty years of WNT signalling research has resulted in a solid blueprint of the pathway and detailed insight into its core working mechanism. However, many details remain incompletely understood, especially in the context of how Wnt signalling drives division and differentiation of stem cells in complex, mammalian tissues. This brings the challenge of studying often subtle signalling events in wholetissue samples. Therefore, in this thesis, we have developed novel tools to study endogenous WNT signalling in mice.