中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (6): 1036-1045.doi: 10.4103/1673-5374.233447

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

RXRα下调是成年蝾螈尾部和尾部脊髓再生所必需的

  

  • 收稿日期:2018-04-09 出版日期:2018-06-15 发布日期:2018-06-15

Retinoid X receptor α downregulation is required for tail and caudal spinal cord regeneration in the adult newt

Sarah E. Walker1, Rachel Nottrodt1, 2, Lucas Maddalena1, 3, Christopher Carter1, 4, Gaynor E. Spencer1, Robert L. Carlone1   

  1. 1 Department of Biological Sciences, Brock University, Ontario, Canada;
    2 Department of Geosciences, University of Calgary, Calgary Alberta, Canada;
    3 Biomedical Sciences, Cambridge University, Cambridge, UK;
    4 Pre-Health Sciences Department, Niagara College, Welland, Ontario, Canada
  • Received:2018-04-09 Online:2018-06-15 Published:2018-06-15
  • Contact: Robert L. Carlone, Ph.D.,rcarlone@brocku.ca.
  • Supported by:

    This study was supported by Natural Sciences and Engineering Council of Canada Discovery Grant to RLC and GES.

摘要:

orcid:0000-0002-5007-2921(Robert L. Carlone)

Abstract:

Some adult vertebrate species, such as newts, axolotls and zebrafish, have the ability to regenerate their central nervous system (CNS). However, the factors that establish a permissive CNS environment for correct morphological and functional regeneration in these species are not well understood. Recent evidence supports a role for retinoid signaling in the intrinsic ability of neurons, in these regeneration-competent species, to regrow after CNS injury. Previously, we demonstrated that a specific retinoic acid receptor (RAR) subtype, RARβ, mediates the effects of endogenous retinoic acid (RA) on neuronal growth and guidance in the adult newt CNS after injury. Here, we now examine the expression of the retinoid X receptor RXRα (a potential heterodimeric transcriptional regulator with RARβ), in newt tail and spinal cord regeneration. We show that at 21 days post-amputation (dpa), RXRα is expressed at temporally distinct periods and in non-overlapping spatial domains compared to RARβ. Whereas RARβ protein levels increase, RXRα proteins level decrease by 21 dpa. A selective agonist for RXR, SR11237, prevents both this downregulation of RXRα and upregulation of RARβ and inhibits tail and caudal spinal cord regeneration. Moreover, treatment with a selective antagonist for RARβ, LE135, inhibits regeneration with the same morphological consequences as treatment with SR11237. Interestingly, LE135 treatment also inhibits the normal downregulation of RXRα in tail and spinal cord tissues at 21 dpa. These results reveal a previously unidentified, indirect regulatory feedback loop between these two receptor subtypes in regulating the regeneration of tail and spinal cord tissues in this regeneration-competent newt.

Key words: retinoid X receptor, spinal cord regeneration, newt, retinoic acid, ependymoglia, retinoic acid receptor