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
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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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