The role of Cited2 in axonal regeneration
File(s)
Author(s)
Mueller, Franziska
Type
Thesis or dissertation
Abstract
Neuronal maturation is characterised as the switch from a neuronal growth to a synapse formation stage and is accompanied by a decreasing neuronal regenerative capacity during development that continues throughout age. A spinal cord injury results in the failure to activate a regenerative programme in mature adult neurons, critically limiting regeneration and functional recovery. Whether neuronal maturation marks the decline in growth competence in the injured mammalian adult nervous system remains elusive. Resulted indicated that gene expression and epigenetic signatures associated with regenerative growth of dorsal root ganglia sensory neurons are lost throughout neuronal maturation and polarisation. The transcriptional co-factor Cited2 was identified and found to be epigenetically upregulated in immature non-polarised DRG neurons and after a regenerative peripheral injury, but not after a non-regenerative spinal cord injury. Overexpressing Cited2 promoted axonal regeneration, reversed gene expression and epigenetic signatures associated with neuronal maturation, and induced the transition towards an immature, non-polarised phenotype in DRG neurons. These results indicate that the transition to a mature state marks the reversible loss of the neuronal regenerative ability and can be manipulated, thus paving the way to targeted repair strategies relaying on neuronal dematuration.
Version
Open Access
Date Issued
2023-01
Date Awarded
2023-06
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Di Giovanni, Simone
Sponsor
Brain Research UK
Grant Number
P73576
Publisher Department
Department of Brain Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)