One of the main objectives of this project was the identification of the cellular and molecular mechanisms allowing brain regeneration to occur in the regeneration-capable adult zebrafish. Towards this goal, we identified radial glia as well as neuroepithelial cells as the predominant source of new neurons in the zebrafish forebrain, cerebellum and retina. Publications: Kaslin et al., Development 2017; Kaslin and Brand, Essentials of Cerebellum and Cerebellar Disorders 2016; Lange et al., Development 2020. Moreover, we used gain- and loss-of-function studies to unravel in particular the function of Thyroglobulin, Lrrk2 and Hippo signaling during homeostasis and regeneration. Publications: Suzzi et al., BioRxiv 2017; Suzzi et al., Plos Genetics 2021. The project also identified acute inflammation as a central and common feature of regeneration across different neural tissues. Publication: Bosak et al., International Journal of Developmental Biology 2018. The second main objective of the project involved the translation of insights from the regeneration-competent zebrafish to the regeneration-incompetent mouse model. This undertaking involved a highly risky endeavor, in which we investigated the ability of the evolutionary conserved genes gata3 and cxcr5 to promote the production of new neurons directly in the lesioned, adult mouse brain. Independent of that, we established an adult mouse astrocyte in vitro cell culture system as an intermediate step to test the potential of candidate genes initially in vitro. This cell culture system shows all features of adult in vivo astrocytes and can be easily cultured as well as manipulated to allow subsequent screening of reprogramming factors. Finally, we set up a high throughput-screening platform to functionally screen for drugs affecting neural regeneration. Publications: Arulmozhivarman et al., Journal of Biomolecular Screening; Arulmozhivarman et al., Scientific Reports 2017.
