Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons
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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-02-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/104069 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850079616626065408 |
|---|---|
| author | Ana Catarina Costa Blanca R Murillo Rita Bessa Ricardo Ribeiro Tiago Ferreira da Silva Patrícia Porfírio-Rodrigues Gabriel G Martins Pedro Brites Matthias Kneussel Thomas Misgeld Monika S Brill Monica M Sousa |
| author_facet | Ana Catarina Costa Blanca R Murillo Rita Bessa Ricardo Ribeiro Tiago Ferreira da Silva Patrícia Porfírio-Rodrigues Gabriel G Martins Pedro Brites Matthias Kneussel Thomas Misgeld Monika S Brill Monica M Sousa |
| author_sort | Ana Catarina Costa |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c8fe5dcb71824a389b86592771aeba7e |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-c8fe5dcb71824a389b86592771aeba7e2025-08-20T02:45:10ZengeLife Sciences Publications LtdeLife2050-084X2025-02-011310.7554/eLife.104069Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axonsAna Catarina Costa0https://orcid.org/0000-0001-5359-1981Blanca R Murillo1Rita Bessa2Ricardo Ribeiro3Tiago Ferreira da Silva4Patrícia Porfírio-Rodrigues5Gabriel G Martins6https://orcid.org/0000-0002-6506-9776Pedro Brites7Matthias Kneussel8https://orcid.org/0000-0003-4900-366XThomas Misgeld9https://orcid.org/0000-0001-9875-6794Monika S Brill10https://orcid.org/0000-0001-5422-9175Monica M Sousa11https://orcid.org/0000-0002-4524-2260Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal; Graduate Program in Molecular and Cell Biology, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, PortugalNerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalNerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalNerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalNeurolipid Biology Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalAdvanced Imaging Unit, Instituto Gulbenkian de Ciência, Lisboa, PortugalAdvanced Imaging Unit, Instituto Gulbenkian de Ciência, Lisboa, PortugalNeurolipid Biology Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalInstitute of Molecular Neurogenetics, Center for Molecular Neurobiology Hamburg, ZMNH, University Medical Centre Hamburg-Eppendorf, Hamburg, GermanyInstitute of Neuronal Cell Biology, Technical University of Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, GermanyInstitute of Neuronal Cell Biology, Technical University of Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, GermanyNerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, PortugalSensory 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.https://elifesciences.org/articles/104069axon growthaxon regenerationcargo sortingconditioning lesiondorsal root ganglionmicrotubules |
| spellingShingle | Ana Catarina Costa Blanca R Murillo Rita Bessa Ricardo Ribeiro Tiago Ferreira da Silva Patrícia Porfírio-Rodrigues Gabriel G Martins Pedro Brites Matthias Kneussel Thomas Misgeld Monika S Brill Monica M Sousa Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons eLife axon growth axon regeneration cargo sorting conditioning lesion dorsal root ganglion microtubules |
| title | Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons |
| title_full | Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons |
| title_fullStr | Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons |
| title_full_unstemmed | Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons |
| title_short | Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons |
| title_sort | axon specific microtubule regulation drives asymmetric regeneration of sensory neuron axons |
| topic | axon growth axon regeneration cargo sorting conditioning lesion dorsal root ganglion microtubules |
| url | https://elifesciences.org/articles/104069 |
| work_keys_str_mv | AT anacatarinacosta axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT blancarmurillo axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT ritabessa axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT ricardoribeiro axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT tiagoferreiradasilva axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT patriciaporfiriorodrigues axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT gabrielgmartins axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT pedrobrites axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT matthiaskneussel axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT thomasmisgeld axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT monikasbrill axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons AT monicamsousa axonspecificmicrotubuleregulationdrivesasymmetricregenerationofsensoryneuronaxons |