Retinoic acid receptor beta2 and neurite outgrowth in the adult mouse spinal cord in vitro.
Retinoic acid, acting through the nuclear retinoic acid receptor beta2 (RARbeta2), stimulates neurite outgrowth from peripheral nervous system tissue that has the capacity to regenerate neurites, namely, embryonic and adult dorsal root ganglia. Similarly, in central nervous system tissue that can regenerate, namely, embryonic mouse spinal cord, retinoic acid also stimulates neurite outgrowth and RARbeta2 is upregulated. By contrast, in the adult mouse spinal cord, which cannot regenerate, no such upregulation of RARbeta2 by retinoic acid is observed and no neurites are extended in vitro. To test our hypothesis that the upregulation of RARbeta2 is crucial to neurite regeneration, we have transduced adult mouse or rat spinal cord in vitro with a minimal equine infectious anaemia virus vector expressing RARbeta2. After transduction, prolific neurite outgrowth occurs. Outgrowth does not occur when the cord is transduced with a different isoform of RARbeta nor does it occur following treatment with nerve growth factor. These data demonstrate that RARbeta2 is involved in neurite outgrowth, at least in vitro, and that this gene may in the future be of some therapeutic use.
Corcoran
Jonathan
J
MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, Guy's Campus, London SE1 1UL, UK. malcolm.maden@kcl.ac.uk
So
Po-Lin
PL
Barber
Robert D
RD
Vincent
Karen J
KJ
Mazarakis
Nicholas D
ND
Mitrophanous
Kyriacos A
KA
Kingsman
Susan M
SM
Maden
Malcolm
M
D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D009416:Nerve Regeneration / Q000235:genetics*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D014161:Transduction, Genetic; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology
D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D014212:Tretinoin