Target contact regulates GAP-43 and ?-tubulin mRNA levels in regenerating retinal ganglion cells

Abstract

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.

A Role for 1 Tubulin-Expressing Muller Glia in Regeneration of the Injured Zebrafish Retina

“…Next, we examined transgene expression after optic nerve crush. As expected, the injured ganglion cells expressed GAP43, which is induced during axon regeneration (Perry et al, 1987;Bormann et al, 1998), but not GFP (supplemental Fig. 1, available at www.…”

An Element in the α1-Tubulin Promoter Is Necessary for Retinal Expression during Optic Nerve Regeneration But Not after Eye Injury in the Adult Zebrafish

“…␣1-Tubulin promoter activity in the axotomized retina of WT, EHD, and HD adult transgenic zebrafish In the adult zebrafish, ␣1-tubulin expression has been shown to accompany regrowth of RGC axons after optic nerve crush (Burrell et al, 1978;Hieber et al, 1998;Bormann et al, 1998;Goldman et al, 2001). To determine to what extent the E-box and HD elements contribute to ␣1-tubulin expression in this nerve regeneration model, we first analyzed and compared the distribution pattern of GFP immunoreactivity in the retinas and optic nerves of WT2 (n ϭ 30), EHD10 (n ϭ 20), and HD2 (n ϭ 26) transgenic fish at various time points after optic nerve crush (Fig.…”

“…4). Successful optic nerve crush was assessed using immunostaining for GAP-43, a protein also expressed by the regenerating RGC axons in the fish (Perry et al, 1987;Bormann et al, 1998). All cases displaying partial nerve crush, as evidenced by a partial GAP-43 immunostaining of the regenerating optic nerve, were discarded from the study.…”

“…Specifically, unlike mammals, the fish CNS displays remarkable regenerative potential in response to injury, which makes it a valuable model for studying successful CNS regeneration in the adult (Bernhardt, 1999). Furthermore, ␣-tubulin is also reexpressed in the regenerating fish CNS after injury (Burrell et al, 1978;Hieber et al, 1992;Bormann et al, 1998).…”

Intrinsic Factors Contributing to Axon Regeneration in the Mammalian Nervous System

“…Retrograde signals may also contribute to regulate neuritic growth in the CNS. The expression of neuronal growth-associated proteins can be influenced by target-derived cues in both developing (Karimi-Abdolrazee and Schreyer, 2002) and adult neurons (Hughes et al, 1997;Bormann et al, 1998;Haas et al, 1998). Furthermore, the same proteins can be up-regulated following the loss of postsynaptic partners (Buffo et al, 2003) or the blockade of axonal transport Zagrebelsky et al, 1998;Buffo et al, 2003).…”