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Integrin-Driven Axon Regeneration in the Spinal Cord Activates a Distinctive CNS Regeneration Program

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F23%3A00580785" target="_blank" >RIV/68378041:_____/23:00580785 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.jneurosci.org/content/43/26/4775" target="_blank" >https://www.jneurosci.org/content/43/26/4775</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1523/JNEUROSCI.2076-22.2023" target="_blank" >10.1523/JNEUROSCI.2076-22.2023</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Integrin-Driven Axon Regeneration in the Spinal Cord Activates a Distinctive CNS Regeneration Program

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30103 - Neurosciences (including psychophysiology)

Result continuities

  • Project

    <a href="/en/project/EF15_003%2F0000419" target="_blank" >EF15_003/0000419: Center of Reconstructive Neuroscience</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2023

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Journal of Neuroscience

  • ISSN

    0270-6474

  • e-ISSN

    1529-2401

  • Volume of the periodical

    43

  • Issue of the periodical within the volume

    26

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    20

  • Pages from-to

    4775-4794

  • UT code for WoS article

    001033553700003

  • EID of the result in the Scopus database

    2-s2.0-85164062750