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

Jordan W. Squair; Marco Milano; Alexandra de Coucy; Matthieu Gautier; Michael A. Skinnider; Nicholas D. James; Newton Cho; Anna Lasne; Claudia Kathe; Thomas H. Hutson; Steven Ceto; Laetitia Baud; Katia Galan; Viviana Aureli; Achilleas Laskaratos; Quentin Barraud; Timothy J. Deming; Richie E. Kohman; Bernard L. Schneider; Zhigang He; Jocelyne Bloch; Michael V. Sofroniew; Gregoire Courtine; Mark A. Anderson

doi:10.1126/science.adi6412

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

Jordan W. Squair, Marco Milano, Alexandra de Coucy, Matthieu Gautier, Michael A. Skinnider, Nicholas D. James, Newton Cho, Anna Lasne, Claudia Kathe, Thomas H. Hutson, Steven Ceto, Laetitia Baud, Katia Galan, Viviana Aureli, Achilleas Laskaratos, Quentin Barraud, Timothy J. Deming, Richie E. Kohman, Bernard L. Schneider, Zhigang HeJocelyne Bloch, Michael V. Sofroniew, Gregoire Courtine, Mark A. Anderson

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1338-1345
Number of pages	8
Journal	Science
Volume	381
Issue number	6664
DOIs	https://doi.org/10.1126/science.adi6412
State	Published - Sep 22 2023
Externally published	Yes

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Squair, J. W., Milano, M., de Coucy, A., Gautier, M., Skinnider, M. A., James, N. D., Cho, N., Lasne, A., Kathe, C., Hutson, T. H., Ceto, S., Baud, L., Galan, K., Aureli, V., Laskaratos, A., Barraud, Q., Deming, T. J., Kohman, R. E., Schneider, B. L., ... Anderson, M. A. (2023). Recovery of walking after paralysis by regenerating characterized neurons to their natural target region. Science, 381(6664), 1338-1345. https://doi.org/10.1126/science.adi6412

@article{8c5264b2e734497f831e4c7add5ce2fc,

title = "Recovery of walking after paralysis by regenerating characterized neurons to their natural target region",

abstract = "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.",

author = "Squair, {Jordan W.} and Marco Milano and {de Coucy}, Alexandra and Matthieu Gautier and Skinnider, {Michael A.} and James, {Nicholas D.} and Newton Cho and Anna Lasne and Claudia Kathe and Hutson, {Thomas H.} and Steven Ceto and Laetitia Baud and Katia Galan and Viviana Aureli and Achilleas Laskaratos and Quentin Barraud and Deming, {Timothy J.} and Kohman, {Richie E.} and Schneider, {Bernard L.} and Zhigang He and Jocelyne Bloch and Sofroniew, {Michael V.} and Gregoire Courtine and Anderson, {Mark A.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2023",

month = sep,

day = "22",

doi = "10.1126/science.adi6412",

language = "English (US)",

volume = "381",

pages = "1338--1345",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6664",

}

Squair, JW, Milano, M, de Coucy, A, Gautier, M, Skinnider, MA, James, ND, Cho, N, Lasne, A, Kathe, C, Hutson, TH, Ceto, S, Baud, L, Galan, K, Aureli, V, Laskaratos, A, Barraud, Q, Deming, TJ, Kohman, RE, Schneider, BL, He, Z, Bloch, J, Sofroniew, MV, Courtine, G & Anderson, MA 2023, 'Recovery of walking after paralysis by regenerating characterized neurons to their natural target region', Science, vol. 381, no. 6664, pp. 1338-1345. https://doi.org/10.1126/science.adi6412

TY - JOUR

T1 - Recovery of walking after paralysis by regenerating characterized neurons to their natural target region

AU - Squair, Jordan W.

AU - Milano, Marco

AU - de Coucy, Alexandra

AU - Gautier, Matthieu

AU - Skinnider, Michael A.

AU - James, Nicholas D.

AU - Cho, Newton

AU - Lasne, Anna

AU - Kathe, Claudia

AU - Hutson, Thomas H.

AU - Ceto, Steven

AU - Baud, Laetitia

AU - Galan, Katia

AU - Aureli, Viviana

AU - Laskaratos, Achilleas

AU - Barraud, Quentin

AU - Deming, Timothy J.

AU - Kohman, Richie E.

AU - Schneider, Bernard L.

AU - He, Zhigang

AU - Bloch, Jocelyne

AU - Sofroniew, Michael V.

AU - Courtine, Gregoire

AU - Anderson, Mark A.

PY - 2023/9/22

Y1 - 2023/9/22

N2 - 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.

AB - 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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SP - 1338

EP - 1345

JO - Science

JF - Science

IS - 6664

ER -

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

Abstract

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