Untangling neural regeneration in vertebrates using an evolutionary systems approach

Non-mammalian vertebrates have an amazing capability to regenerate their brain and spinal cord. In contrast, mammals very poorly regenerate their brain or spinal cord. The inability to repair the brain or spinal cord is a significant clinical issue with wide-reaching social and economic effects. In this project, we use an evo-devo approach involving different vertebrate models to determine the underlying cellular and genetic drivers of neural regeneration in the vertebrate lineage. CNS regeneration in vertebrates follow a general phylogenetic trend with mammals as poor regenerators and fish/amphibians as highly regenerative but this has not been systematically studied and the underlying cellular and genetic basis is not well understood. To understand how the ability to regenerate spinal cord has changed between species (shark, fish, amphibian, reptile, bird and mammalian) during evolution we will study pivotal cell types and genes in key representative species in the vertebrate lineage using the highly regenerative zebrafish as basic node for comparison. Furthermore, the available genomes and genome editing tools using CRISPR/Cas allows for in depth bioinformatics and functional validation of identified genes or genomic loci.