TARGET CONTACT REGULATES GAP-43 AND ALPHA-TUBULIN MESSENGER-RNA LEVELS IN REGENERATING RETINAL GANGLION-CELLS

Axotomy of vertebrate neurons leads to the transient upregulation of G AP-43 and alpha-tubulin. In adult zebrafish retina, mRNA levels of bot h genes were increased in retinal ganglion cells after optic nerve les ion following a similar time course, At 5 days after crush, the mRNA l evel of GAP-43 was increased nearly 20 times, whereas a 6-fold increas e was observed for alpha-tubulin. Subsequently, upon target reinnervat ion, mRNA levels of both genes were downregulated and were 2-fold high er than normal at 25 days after crush. Stretching the optic nerve that results in diffuse axonal lesions led to the expression of both genes in identical subsets of retinal ganglion cells. When regeneration was prevented by removing a piece of the optic nerve, mRNA levels remaine d elevated. Disruption of axonal transport by colchicine and vinblasti ne led to the induction of both genes in normal retina. Blocking elect rical activity with tetrodotoxin had no effect, This indicates that re trogradely transported signals induced by target contact regulate GAP- 43 and alpha-tubulin transcription. Furthermore, the joint regulation of GAP-43 and alpha-tubulin mRNA levels after different kinds of lesio n suggests that a common pathway underlies the regulation of neuronal GAP-43 and alpha-tubulin gene expression, In contrast, distinct mechan isms may control the extent and maintenance of increased mRNA levels o f these genes. (C) 1998 Wiley-Liss, Inc.