Target contact regulates GAP-43 and alpha-tubulin mRNA levels in regenerating retinal ganglion cells.
Axotomy of vertebrate neurons leads to the transient upregulation of GAP-43 and alpha-tubulin. In adult zebrafish retina, mRNA levels of both genes were increased in retinal ganglion cells after optic nerve lesion following a similar time course. At 5 days after crush, the mRNA level of GAP-43 was increased nearly 20 times, whereas a 6-fold increase was observed for alpha-tubulin. Subsequently, upon target reinnervation, mRNA levels of both genes were downregulated and were 2-fold higher 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 remained elevated. Disruption of axonal transport by colchicine and vinblastine led to the induction of both genes in normal retina. Blocking electrical activity with tetrodotoxin had no effect. This indicates that retrogradely 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 lesion suggests that a common pathway underlies the regulation of neuronal GAP-43 and alpha-tubulin gene expression. In contrast, distinct mechanisms may control the extent and maintenance of increased mRNA levels of these genes.
Bormann
P
P
Department of Pharmacology, Biozentrum, University of Basel, Switzerland.
Zumsteg
V M
VM
Roth
L W
LW
Reinhard
E
E
D000818:Animals; D003599:Cytoskeleton / Q000502:physiology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D019922:GAP-43 Protein / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D007536:Isomerism; D008969:Molecular Sequence Data; D009416:Nerve Regeneration / Q000235:genetics*; D009900:Optic Nerve / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D014404:Tubulin / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D015027:Zebrafish
D018076:DNA, Complementary; D019922:GAP-43 Protein; D012333:RNA, Messenger; D014404:Tubulin