Differential expression of immediate early genes after transection of the facial nerve

Facial motoneurons respond to peripheral transection of the facial nerve with a number of molecular changes. In order to obtain insight into the transcriptional mechanisms underlying the changes induced by axotomy, the expression of a number of immediate early genes was investigated after facial nerve lesion in the rat. Some immediate early genes (such as c-fos, c-jun or jun B) are known to encode transcription factors that bind to DNA at sites that regulate gene expression and they could therefore contribute to long-term changes in motoneurons. Northern blot analysis of RNA extracted from the facial nucleus from postoperative intervals covering hours and days revealed that axotomy results in a unique pattern of immediate early gene induction in the facial nucleus. c-Jun, jun B and 12-O-tetradecanoylphorbol-13-acetate-induced sequence (TIS) 11 messenger RNA, also present in low amounts in the unoperated nucleus, were strongly induced in a long-term fashion after nerve injury. Increased levels of these messenger RNAs were first detectable at 5 h, reaching a maximum (300-500% compared to control) within 24 h followed by a gradual decline during the following week. Elevated levels were maintained at least up to eleven days compared to the unoperated side. On the other hand, c-fos messenger RNA was neither expressed in the unoperated nucleus, nor was c-fos messenger RNA induced by axotomy at any of the time-points studied. Another member of the TIS family of immediate early genes TIS 7 (PC4), however, was detectable at low levels in normal facial nucleus, but its expression was unaffected by lesion. The three axotomy-induced messenger RNAs, c-jun, jun B and TIS 11, were all localized in the facial motoneurons by in situ hybridization histochemistry indicating that their induction occurs as part of the retrograde reaction of the motoneurons in response to lesion. These data suggest that c-jun, jun B and TIS 11 may play a role in triggering the regeneration programme of motoneurons.