Motor neuron regeneration in larval zebrafish

Zebrafish, in contrast to mammals, regenerate spinal motor neurons. Previous work on spinal-lesioned adult zebrafish has led to important insights into the signals that allow spinal progenitor cells to produce new motor neurons after injury and in human embryonic stem cell culture. In order to replace animal experiments with a substantial severity banding and to significantly speed up experiments, we suggest to develop protocols for spinal lesions in larval zebrafish, most of which are completed before larvae become protected under the Animals (Scientific Procedures) Act 1986. We hypothesise that larval spinal lesion paradigms reproduce the salient features of adult lesions and lead to the discovery of differentiation pathways that are relevant for human stem cell differentiation. Therefore, the PhD student will 1) demonstrate that pathways known from adult regeneration have similar effects in larval regeneration; 2) establish a genetic lesion paradigm for motor neurons; 3) test pathways that are effective in zebrafish motor neuron regeneration and in motor neuron differentiation from human embryonic stem cells. This project will lead to the replacement of up to 400 fish currently undergoing procedures of substantial severity in our laboratory alone, and has the potential to reduce the number of CNS procedures (420,000 per year) overall. Data from this project will improve our understanding of vertebrate motor neuron (re-) eneration, and may ultimately contribute to therapeutic approaches to motor neuron disease and spinal cord injury.

Tsarouchas TM et al. (2018). Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration. Nature communications 9(10):4670. doi: 10.1038/s41467-018-07036-w

Cardozo MJ et al. (2017). Reduce, reuse, recycle - Developmental signals in spinal cord regeneration. Developmental biology 432(1):52-62. doi: 10.1016/j.ydbio.2017.05.011

Wehner D et al. (2017). Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish. Nature Communications 8(1):126. doi: 10.1038/s41467-017-00143-0

Ohnmacht J et al. (2016). Spinal motor neurons are regenerated after mechanical lesion and genetic ablation in larval zebrafish. Development 143:1464-1474. doi: 10.1242/dev.129155 

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PhD Studentship

Status:

Closed

Principal investigator

Professor Catherina Becker

Institution

University of Edinburgh

Co-Investigator

Dr Thomas Becker

Grant reference number

NC/L001063/1

Award date:

Nov 2014 - Nov 2017

Grant amount

£90,000