Epigenetic regulation of neuronal regeneration after spinal cord lesion in zebrafish

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In contrast to mammals, zebrafish regenerate spinal neurons after injury (Becker and Becker, 2015).These new neurons replace lost ones and act as relays to bring about functional recovery. This is never observed in mammals. It is therefore important to determine how gene expressionprogrammes change in spinal progenitor cells after injury to allow for neurogenesis in zebrafish. In this PhD project in the Becker group (Edinburgh), the student will elucidate the epigeneticdeterminants of regenerative neurogenesis. The Becker group have established an efficient larval regeneration paradigm (Wehner et al., 2017) and preliminary observations indicate that epigenetichistone acetylation levels are altered after a lesion. Low acetylation levels are necessary for proper regeneration of motor neurons.AimsBased on these functional data the student will use bioinformatics approaches with the MacKenzie group (Aberdeen) to identify target sequences and downstream genes of these alterations ofacetylation (Hay et al., 2017). The importance of downstream genes will then be verified by in vivo perturbation experiments in zebrafish using CRISPR/Cas9 knock out and cell-type specific over- expression using the TetOn system. The student will work with a postdoc Dr Leonardo Cavone,funded by a new BBSRC project grant (to Thomas Becker, start date 15.10.2017).With this line of research, we hope to elucidate the intrinsic changes in spinal stem cells necessary for successful spinal cord regeneration. This project will provide targets for manipulations in endogenousmammalian stem cells, which invariably fail to generate neurons after injury.