AXONAL REGROWTH UP-REGULATES BETA-ACTIN AND JUN-D MESSENGER-RNA EXPRESSION

When quiescent cells are perturbed, mRNAs encoding proteins that regul ate gene transcription and the cell cycle are expressed at higher leve ls. Jun and Fos are examples of proteins that mediate mitogenic signal s and influence differentiation. In neurons, axon interruption (axotom y) increases the content of actin, tubulin, Jun D, and c-Jun proteins in association with increases in actin mRNA levels. Jun D protein bind s to gene promoter regions, and its expression has been linked to seve ral aspects of cell differentiation. Because Jun D and beta-actin mess ages 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 Spra gue-Dawley rats and extracted mRNA from the half spinal cord that serv es each leg. At 4 days, Northern blots showed a 2.3-fold increase in b eta-actin mRNA and a 2.5-fold increase in Jun D mRNA in the right hemi cord. In situ hybridization showed either an undiminished or increased concentration of both mRNAs in motor neurons ipsilateral to the lesio n at 4 days, even though many had enlarged two-to threefold. By introd ucing Fluoro-Ruby at the axotomy site, we were able to show that only the axotomized neurons had enlarged. We conclude that aspects of axona l regeneration resemble the embryonic program for neuronal differentia tion and are reinitiated by axotomy. (C) 1996 John Wiley & Sons, Inc.