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Integrin-Driven Axon Regeneration in the Spinal Cord Activates a Distinctive CNS Regeneration Program
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SYSNO ASEP 0580785 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Integrin-Driven Axon Regeneration in the Spinal Cord Activates a Distinctive CNS Regeneration Program Author(s) Cheah, M. (GB)
Cheng, Y. (US)
Petrová, V. (US)
Cimpean, Anda (UEM-P)
Jendelová, Pavla (UEM-P) RID, ORCID
Swarup, V. (US)
Woolf, C.J. (US)
Geschwind, D.H. (US)
Fawcett, James (UEM-P) ORCIDSource Title Journal of Neuroscience. - : Society for Neuroscience - ISSN 0270-6474
Roč. 43, č. 26 (2023), s. 4775-4794Number of pages 20 s. Language eng - English Country US - United States Keywords autophagy ; axon regeneration ; integrin ; sensory ; signaling ; spinal cord OECD category Neurosciences (including psychophysiology R&D Projects EF15_003/0000419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UEM-P - RVO:68378041 UT WOS 001033553700003 EID SCOPUS 85164062750 DOI 10.1523/JNEUROSCI.2076-22.2023 Annotation The peripheral branch of sensory dorsal root ganglion (DRG) neurons regenerates readily after injury unlike their central branch in the spinal cord. However, extensive regeneration and reconnection of sensory axons in the spinal cord can be driven by the expression of a9 integrin and its activator kindlin-1 (a9k1), which enable axons to interact with tenascin-C. To elucidate the mechanisms and downstream pathways affected by activated integrin expression and central regeneration, we conducted transcriptomic analyses of adult male rat DRG sensory neurons transduced with a9k1, and controls, with and without axotomy of the central branch. Expression of a9k1 without the central axotomy led to upregulation of a known PNS regeneration program, including many genes associated with peripheral nerve regeneration. Coupling a9k1 treatment with dorsal root axotomy led to extensive central axonal regeneration. In addition to the program upregulated by a9k1 expression, regeneration in the spinal cord led to expression of a distinctive CNS regeneration program, including genes associated with ubiquitination, autophagy, endoplasmic reticulum (ER), trafficking, and signaling. Pharmacological inhibition of these processes blocked the regeneration of axons from DRGs and human iPSC-derived sensory neurons, validating their causal contributions to sensory regeneration. This CNS regeneration-associated program showed little correlation with either embryonic development or PNS regeneration programs. Potential transcriptional drivers of this CNS program coupled to regeneration include Mef2a, Runx3, E2f4, and Yy1. Signaling from integrins primes sensory neurons for regeneration, but their axon growth in the CNS is associated with an additional distinctive program that differs from that involved in PNS regeneration. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2024 Electronic address https://www.jneurosci.org/content/43/26/4775
Number of the records: 1