Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons
Year: 2024
Type: preprint
Abstract: Sensory dorsal root ganglion (DRG) neurons have a unique pseudo-unipolar morphology in which a stem axon bifurcates into a peripheral and a central axon, with different regenerative abilities. Whereas peripheral DRG axons regenerate, central axons are unable to regrow. Central axon regeneration can however be elicited by a prior conditioning lesion to the peripheral axon. How DRG axon asymmetry is established remains unknown. Here we developed a rodent in vitro system replicating DRG pseudo-unipolarization and asymmetric axon regeneration. Using this model, we observed that from early development, central DRG axons have a higher density of growing microtubules. This asymmetry was also present in vivo and was abolished by a conditioning lesion that decreased microtubule polymerization of central DRG axons. An axon-specific microtubule-associated protein (MAP) signature, including the severases spastin and katanin and the microtubule regulators CRMP5 and tau, was found and shown to adapt upon conditioning lesion. Supporting its significance, interfering with the DRG MAP signature either in vitro or in vivo readily abolished central-peripheral asymmetries in microtubule dynamics and regenerative ability. In summary, our data unveil that axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons.
Source: eLife
DOI: 10.7554/elife.104069
Institutions: Universidade do Porto, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Instituto de Biologia Molecular e Celular, Instituto de Ciências Biomédicas Albel Salazar, Instituto Gulbenkian de Ciência, University Medical Center Hamburg-Eppendorf, Munich Cluster for Systems Neurology, Technical University of Munich
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Mikrotubulimodifikationen und severing regulieren axonales Remodeling während der neuromuskulären Synapsenelimination, G1516346500, G1636457746, G1763632427, G1789099517, G1993314343, G2195151728, Unraveling the role of the microtubule cytoskeleton in DRG axonal asymmetry and regenerative capacity, G3199322896, G3382598596, G3840324753, EXC 2145: Munich Cluster for Systems Neurology (SyNergy), Unraveling the role of the microtubule cytoskeleton in DRG axonal asymmetry and regenerative capacity, G5224927334, G5544290840, G5585317864, G7584003722, Adaptações do citoesqueleto e membrana de axónios em tensão: do alongamento induzido por stretch às lesões traumáticas cerebrais, G862925997
OpenAlex ID: W4404859931