Characterization of the interaction of a purinergic receptor in regulation of WNT/β-catenin signaling pathway using zebrafish model

Wnt/β-catenin signalling pathway has essential roles in development, neural growth, differentiation and regeneration. Therefore, malfunctioning in the pathway has been associated with different types of cancer, genetic diseases and neurodegenerative disorders. Although most studies enlighten the pathway components, there are still unknown about its detailed regulation. Detailed research about Wnt signalling pathway and its mechanism will reveal pathway's critical roles in diseases. In our studies, the interaction between Wnt/β-catenin signalling pathway and purinergic receptors, which their significant role is known in synaptic transmission and regeneration, is investigated. Zebrafish p2rx8 and p2rx5 genes, which are chosen candidates from RNA sequencing data for regulation of Wnt/β-catenin signalling pathway, were investigated in development. It was observed that Wnt/β-catenin signalling pathway is inhibited when zebrafish p2rx5 gene is overexpressed and it is necessary for proper somitogenesis during the development. Then, all identified P2X purinergic receptors were investigated and it was observed that overexpression of p2rx1, p2rx3a, p2rx5, p2rx7 genes inhibits Wnt/β-catenin signalling pathway activity in both embryos and cell culture. Lastly, we started to generate Tg(hsp70l:p2rx3a:EGFP) and Tg(hsp70l:p2rx7:EGFP) transgenic zebrafish lines in order to investigate the interaction between Wnt/β-catenin signalling pathway and purinergic receptors in zebrafish caudal fin regeneration. Our study demonstrated that purinergic receptors, associated with their important roles in neurodegenerative diseases, are novel targets of Wnt/β-catenin signalling pathway and they also act as a negative feedback regulator. We aimed with this findings to contribute to understand better the mechanism of neurodegenerative diseases such as Alzheimer and develop new therapies.