creating a
healthier future

Nerve Regeneration

ABOUT

The Nerve Regeneration group aims to explore the pathways that regulate axon growth during development and facilitate axon regeneration after injury, with a particular emphasis on the axonal cytoskeleton. Additionally, we recently identified the spiny mouse as the first known mammal capable of spontaneous spinal cord regeneration and are currently investigating the underlying mechanisms behind this remarkable ability.

 

RESEARCH

Neurons are among the most strikingly polarized eukaryotic cells, relying on cytoskeletal dynamics to shape their unique structure and function. Understanding the basic neuronal cell biology is essential for uncovering mechanisms underlying neurodegeneration and developing strategies to enhance axon regeneration. In this context, our group focuses on the following key research areas:

  1. Understanding the formation and function of the axonal membrane periodic skeleton;and
  2. Unraveling how sensory neuron axons establish central-peripheral polarity.

In adult mammals, central nervous system injuries typically result in scar tissue formation, preventing regeneration. However, our group has shown that the spiny mouse is capable of spontaneous spinal cord repair after transection. We now aim to uncover the mechanisms that enable this unique regenerative ability.

Our research integrates in vitro neuronal cell culture systems with in vivo rodent models, including spinal cord injury and rare neurodegenerative disorder models, and combines genetic strategies, cell biology, advanced microscopy and transcriptomics.

Team

Selected Publications

Costa A.C., Murillo B.R., Bessa R., Ribeiro R., Ferreira da Silva T., Porfírio-Rodrigues P., Martins G.G., Brites P., Kneussel M., Misgeld T., Brill M.S., Sousa M.M.
Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons. eLife13:, 2025. [Journal: Article] [IF: 6.4 (*)]
DOI: 10.7554/eLife.104069 SCOPUS: 85219648556

Sousa S.C., Aroso M., Bessa R., Veríssimo E., Silva T., Lopes C.D.F., Brites P., Vieira J., Vieira C.P., Aguiar P.C., Sousa M.M.
Stretch triggers microtubule stabilization and MARCKS-dependent membrane incorporation in the shaft of embryonic axons. Current Biology34(19):4577-4588.e8, 2024. [Journal: Article] [IF: 8.1 (*)]
DOI: 10.1016/j.cub.2024.08.018 SCOPUS: 85206018898

Brites P., Sousa M.M.
Neurons contribute to pathology in a mouse model of Krabbe disease in a cellautonomous manner. PLoS Biology20(7):, 2022. [Journal: Article] [CI: 2] [IF: 9,8]
DOI: 10.1371/journal.pbio.3001706 SCOPUS: 85134360903

Nascimento A.I., Da Silva T.F., Fernandes E.C., Luz L.L., Mar F.M., Safronov B.V., Sousa M.M.
Sensory neurons have an axon initial segment that initiates spontaneous activity in neuropathic pain. Brain145(5):1632-1640, 2022. [Journal: Article] [CI: 11] [IF: 14,5]
DOI: 10.1093/brain/awac078 SCOPUS: 85131702538

Nogueira-Rodrigues J., Leite S.C., Pinto-Costa R., Sousa S.C., Luz L.L., Sintra M.A., Oliveira R., Monteiro A.C., Pinheiro G.G., Vitorino M., Silva J.A., Simão S., Fernandes V.E., Provazník J., Benes V., Cruz C.D., Safronov B.V., Magalhães A., Reis C.A., Vieira J., Vieira C.P., Tiscórnia G., Araújo I.M., Sousa M.M.
Rewired glycosylation activity promotes scarless regeneration and functional recovery in spiny mice after complete spinal cord transection. Developmental Cell57(4):440-450.e7, 2022. [Journal: Article] [CI: 30] [IF: 11,8]
DOI: 10.1016/j.devcel.2021.12.008 SCOPUS: 85123830565

Pinto-Costa R., Sousa S.C., Leite S.C., Nogueira-Rodrigues J., da Silva T.F., Machado D., Marques J., Costa A.C., Liz M.A., Bartolini F., Brites P., Costell M., Fässler R., Sousa M.M.
Profilin 1 delivery tunes cytoskeletal dynamics toward CNS axon regeneration. Journal of Clinical Investigation130(4):2024-2040, 2020. [Journal: Article] [CI: 29] [IF: 14,8]
DOI: 10.1172/JCI125771 SCOPUS: 85082814702

Costa A.R., Sousa S.C., Pinto-Costa R., Mateus J.C., Lopes C.D.F., Costa A.C., Rosa D., Machado D., Pajuelo L., Wang X., Zhou F.Q., Pereira A.J., Sampaio P., Rubinstein B.Y., Pinto I.M., Lampe M., Aguiar P., Sousa M.M.
The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction. eLife9:, 2020. [Journal: Article] [CI: 50] [IF: 8,1]
DOI: 10.7554/eLife.55471 SCOPUS: 85082635132

Ongoing Projects

Cytoskeletal and membrane adaptations of stretched neurons: from tension-induced growth to traumatic brain injury
Reference: DRI/India/0336/2020
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 14-AUG-22 to 13-AUG-25
Translating Acomys Regenerative Capacity
Reference: Premio Melo e Castro - SCML 2022 - TARGET
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Santa Casa da Misericórdia de Lisboa
From 01-JAN-23 to 31-DEC-25
Exploring the proteoglycan signature as a roadmap for mammalian axon regeneration
Reference: AOS-Startup-23-033
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: AO Foundation
From 01-SEP-23 to 31-AUG-25
A human sensory neuron model to explore the pathophysiology of Transthyretin Amyloid Polyneuropathy
Reference: Pfizer GMG 2023-Tracking#87074543
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Pfizer, Inc
From 01-JAN-24 to 31-DEC-25
Exploring the biogenesis, assembly and dynamics of the membrane-periodic skeleton (MPS) in fixed and live systems.
Reference: 2023.00048.RESTART
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 23-DEC-23 to 22-MAY-25
Actin Rings and Actin Pearls: Deciphering their prevalence, relevance and function for the neuron
Reference: 2023.12987.PEX
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 20-FEB-25 to 19-AUG-26