Cellular and molecular mechanisms of axonal regeneration
Injuries to the nervous system can cause lifelong disabilities due to ineffective repair of the damaged nerve fibres and thus, understanding the basic molecular mechanisms regulating axonal regeneration is essential for the development of effective therapies. Using UV-laser axotomy, we are able to sever individual axons in C. elegans to study their responses to injury. We study a highly efficient mechanism of axonal regeneration known as axonal fusion, whereby a regenerating axon is able to reconnect and fuse with its detached segment to restore the original axonal tract and re-establish connection with its target tissue.
We have demonstrated that molecules previously found to function in the recognition of dying cells by phagocytes, also mediate the reconnection between a regrowing axon and its separated segment. We are now studying the precise mechanisms of this recognition process that allow axonal fusion to occur.
Representative Publications
Neumann B*, Linton C, Giordano-Santini R, Hilliard MA (2019). Axonal fusion: an alternative and efficient mechanism of nerve repair. Progress in Neurobiology - Review Feb; 173: 88-101. Journal link.
*First and corresponding author.
*First and corresponding author.
Linton C, Riyadh MA, Ho XY, Neumann B, Giordano-Santini R, Hilliard MA (2019). Disruption of RAB-5 increases EFF-1 fusogen availability at the cell surface and promotes the regenerative axonal fusion capacity of the neuron. Journal of Neuroscience 39 (15) 2823-2836. Journal link. Cover image. bioRxiv version.
Abay ZC, Wong MYY, Teoh JS, Vijayaraghavan T, Hilliard MA, and Neumann B (2017). Phosphatidylserine ‘save-me’ signals drive functional recovery of severed axons in Caenorhabditis elegans. Proceedings of the National Academy of Sciences 114(47): E10196–E10205. Journal link. Media release. Brief summary. Champagne celebrations!
Neumann B, Coakley S, Giordano-Santini R, Linton C, Lee ES, Nakagawa A, Xue D, and Hilliard MA (2015). EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway. Nature 517(7533): 219-222. PubMed link.
Cover image. Faculty of 1000 recommendation.
Cover image. Faculty of 1000 recommendation.