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research article

Recovery of walking after paralysis by regenerating characterized neurons to their natural target region

Squair, Jordan W.  
•
Milano, Marco  
•
de Coucy, Alexandra
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September 22, 2023
Science

Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing to identify neuronal subpopulations that restore walking after incomplete SCI. We show that chemoattracting and guiding the transected axons of these neurons to their natural target region led to substantial recovery of walking after complete SCI in mice, whereas regeneration of axons simply across the lesion had no effect. Thus, reestablishing the natural projections of characterized neurons forms an essential part of axon regeneration strategies aimed at restoring lost neurological functions.

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Type
research article
DOI
10.1126/science.adi6412
Web of Science ID

WOS:001100654900033

Author(s)
Squair, Jordan W.  
Milano, Marco  
de Coucy, Alexandra
Gautier, Matthieu  
Skinnider, Michael Alexander  
James, Nicholas David  
Cho, Newton  
Lasne, Anna  
Kathe, Claudia  
Hutson, Thomas Haynes  
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Date Issued

2023-09-22

Publisher

American Association for the Advancement of Science

Published in
Science
Volume

381

Issue

6664

Start page

1338

End page

1345

Subjects

Central-Nervous-System

•

Spinal-Cord

•

Brain-Stem

•

Circuit Reorganization

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Axonal Regeneration

•

Synapse Formation

•

Growth

•

Motor

•

Organization

•

Cells

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

FunderGrant Number

Bertarelli Platform for Gene Therapy at the School of Life Sciences of EPFL

Available on Infoscience
February 20, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/204649
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