Thesis defense Christa van der Veen: “Regulation of Wnt signal transduction”

To create an entire organism, the first cell has to multiply over and over again. Subsequently, the cells need to be guided in order to find their destination and get to know their specialization. The Wnt pathway plays an important role in this process. This starts with the binding of the Wnt protein to a receptorA protein that serves as a binding place for other proteins. The binding of a protein to the receptor initiates a specific reaction in the cell. on the membrane of the cell. Most often, this results in the activation of either the ‘canonical’ or the ‘non-canonical’ signaling cascade. The first, the ‘canonical’ cascade, influences the activation of certain parts of the DNA. On the contrary, the ‘non-canonical’ cascade regulates the cytoskeletonThe skeleton of the cell. The cytoskeleton determines the shape of the cell and can cause the cell to migrate in a specific direction. which can cause the cell to move. During her PhD, Van der Veen aimed to get a better view on Wnt signaling. In particular, she studied the non-canonical Ror receptor in C. elegans, a small roundworm that is often used in fundamental research.

Surprising result

The Ror receptor is a part of the non-canonical signaling cascade, thus influencing the cytoskeleton. Van der Veen studied this receptor in order to determine its exact role in the migration of cells and the determination of their function. She found out that activation of Ror did not only lead to movement of the cells, but also to the spread of Wnt proteins. Specifically, this was true for two specific Wnt proteins that move to the rear end of C. elegans. Van der Veen: “It was actually quite surprising that we found out that Ror receptors not only affect cell migration, but also the spread of proteins. This could be of importance in cancer research, since Ror has been found to promote tumor growth.”

In addition, Van der Veen studied Hox transcription factorsProteins that activate certain genes by binding to the DNA. Specifically, the activation of these genes results in the migration of the cells to the rear end of the worm. Furthermore, the researchers found that Hox proteins affect the activity of certain components of the Wnt signalling cascade, although they are not a part of the Wnt pathway themselves.

Celebration

Van der Veen describes her PhD trajectory as a ‘mix of mostly positive but also some negative results’. She mentions several highlights: “One of the highlights was definitely the International Worm meeting I attended in Los Angeles. Also, all the people I have met at activities and borrels have really made my time at the Hubrecht Institute a lot of fun!”

Now that her time at the Hubrecht Institute has ended, Van der Veen will celebrate obtaining her doctorate: “My defense and my birthday happen to be very close to each other, so I plan to have a party with friends and family celebrating both occasions at the same time.”