Axonal regrowth upregulates beta-actin and Jun D mRNA expression.
When quiescent cells are perturbed, mRNAs encoding proteins that regulate gene transcription and the cell cycle are expressed at higher level. Jun and Fos are examples of proteins that mediate mitogenic signals and influence differentiation. In neurons, axon interruption (axotomy) increases the content of actin, tubulin, Jun D, and c-Jun proteins in association with increases in actin mRNA levels. Jun D protein binds to gene promoter regions, and its expression has been linked to several aspects of cell differentiation. Because Jun D and beta-actin messages have been described as "constitutive" in expression, we wanted to know whether these messages were responsive to axotomizing lesions of the sciatic motor nerve. We crushed the right sciatic nerve in Sprague-Dawley rats and extracted mRNA from the half spinal cord that serves each leg. At 4 days, Northern blots showed a 2.3-fold increase in beta-actin mRNA and a 2.5-fold increase in Jun D mRNA in the right hemicord. In situ hybridization showed either an undiminished or increased concentration of both mRNAs in motor neurons ipsilateral to the lesion at 4 days, even though many had enlarged two-to threefold. By introducing Fluoro-Ruby at the axotomy site, we were able to show that only the axotomized neurons have enlarged. We conclude that aspects of axonal regeneration resemble the embryonic program for neuronal differentiation and are reinitiated by axotomy.
Lund
L M
LM
VA Medical Center (151 W), Cleveland, Ohio 44106, USA.
McQuarrie
I G
IG
D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D001369:Axons / Q000502:physiology*; D015152:Blotting, Northern; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D017403:In Situ Hybridization; D009409:Nerve Crush; D009412:Nerve Fibers / Q000502:physiology; D009416:Nerve Regeneration; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic
D000199:Actins; D005904:Glial Fibrillary Acidic Protein; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases