B‐50/GAP43 Expression Correlates with Process Outgrowth in the Embryonic Mouse Nervous System

Biffo, Stefano; Verhaagen, Joost; Schrama, Loes H.; Schotman, P.; Danho, Waleed; Margolis, F. L.

doi:10.1111/j.1460-9568.1990.tb00440.x

Cited by 112 publications

(59 citation statements)

References 63 publications

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“…At 7 weeks after ON crush, approximately 6.5% of surviving RGCs extended bIIItubulin + axons at least 0.5 mm distal to the site of injury, and nearly 25% of these had regenerated further than 1.5 mm along the distal ON. Immunostaining with GAP43, a marker for regenerating axons, 55 confirmed this extensive regrowth in AAV-CNTF-GFP treated rats. The number of regenerating RGC axons seen in the present study is similar to the number induced to regrow after ocular macrophage activation 16 or after lens injury and AAV-mediated inactivation of RhoA.…”

Section: Rgc Survival and Regeneration Following On Crushmentioning

confidence: 73%

“…Unlike secretory neuroactive proteins, GAP43 would only affect the transduced cells themselves and the protein can only be effective if cells survive the initial insult. GAP43 has an important role in promoting neurite outgrowth 23,24,55 but it is not a survival factor per se, indeed prolonged over-expression of GAP43 in other CNS neurons can sometimes induce cell death. 60 …”

Section: Cntf Gene Therapy and Visual System Repair Sg Leaver Et Almentioning

confidence: 99%

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AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells

et al. 2006

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We compared the effects of intravitreal injection of bicistronic adeno-associated viral (AAV-2) vectors encoding enhanced green fluorescent protein (GFP) and either ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF) or growth-associated protein-43 (GAP43) on adult retinal ganglion cell (RGC) survival and regeneration following (i) optic nerve (ON) crush or (ii) after ON cut and attachment of a peripheral nerve (PN). At 7 weeks after ON crush, quantification of bIII-tubulin immunostaining revealed that, compared to AAV-GFP controls, RGC survival was not enhanced by AAV-GAP43-GFP but was increased in AAV-CNTF-GFP (mean RGCs/retina: 17 4507358 s.e.m.) and AAV-BDNF-GFP injected eyes (10 20074064 RGCs/ retina). Consistent with increased RGC viability in AAV-CNTF-GFP and AAV-BDNF-GFP injected eyes, these animals possessed many bIII-tubulin-and GFP-positive fibres proximal to the ON crush. However, only in the AAV-CNTF-GFP group were regenerating RGC axons seen in distal ON (11357367 axons/nerve, 0.5 mm post-crush), some reaching the optic chiasm. RGCs were immunoreactive for CNTF and quantitative RT-PCR revealed a substantial increase in CNTF mRNA expression in retinas transduced with AAV-CNTF-GFP. The combination of AAV-CNTF-GFP transduction of RGCs with autologous PN-ON transplantation resulted in even greater RGC survival and regeneration. At 7 weeks after PN transplantation there were 27 954 (72833) surviving RGCs/retina, about 25% of the adult RGC population. Of these, 13 352 (71868) RGCs/retina were retrogradely labelled after fluorogold injections into PN grafts. In summary, AAV-mediated expression of CNTF promotes long-term survival and regeneration of injured adult RGCs, effects that are substantially enhanced by combining gene and cell-based therapies/interventions.

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Section: Rgc Survival and Regeneration Following On Crushmentioning

confidence: 73%

Section: Cntf Gene Therapy and Visual System Repair Sg Leaver Et Almentioning

confidence: 99%

AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells

et al. 2006

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“…Zheng and others suggested that intra-axonal translation of cytoskeletal components was required for sustaining growth cones in regenerating axons (Zheng et al, 2001). GAP43 is a membrane-and cytoskeletal-associated phosphoprotein (Benowitz and Routtenberg, 1987;Skene, 1989;Coggins and Zwiers, 1991) that is expressed at high levels in neurons during development and is concentrated in axonal growth cones (Biffo et al, 1990;Fitzgerald et al, 1991). After neural injury in the adult, however, GAP43 is re-expressed and is rapidly transported along the axons of those neurons where there is successful regeneration (Bisby, 1988;Tetzlaff et al, 1989;Van der Zee et al, 1989;Woolf et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Expression of SSeCKS in Injured Rat Sciatic Nerve

Chen

Qin

Cheng

et al. 2008

The Anatomical Record

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SSeCKS (src suppressed C kinase substrate) functions in the control of cell signaling and cytoskeletal arrangement. It is expressed in brain and spinal cord, but little is known about its expression in peripheral nerves. In this study, in rats, real-time polymerase chain reaction and Western blot analysis showed that expression of SSeCKS in crushed sciatic nerve reached its highest level 6 hr after crushing, whereas in a transection model, SSeCKS peaked at 2 days in the proximal stump and 12 hr in the distal stump. Immunohistochemical analysis demonstrated up-regulation of SSeCKS protein surrounding the crush site and in the two stumps of the transected nerve. In addition, SSeCKS colocalized with growth-associated protein 43 and with S100, which also changed with time after injury. These findings support the idea that SSeCKS participates in the adaptive response to peripheral nerve injury and may be associated with regeneration. Anat Rec, 291:527-537, 2008Rec, 291:527-537, . 2008 Wiley-Liss, Inc.Key words: SSeCKS; sciatic nerve; crush; transect; rat Src suppressed C kinase substrate (SSeCKS) is a high molecular mass (290/280 kDa) heat-stable protein that was identified as a protein kinase C (PKC) substrate/ PKC-binding protein. In vitro, SSeCKS mRNA and protein levels are down-regulated in transformed cells, suggesting a role in growth regulation (Chapline et al., 1996). In vivo, SSeCKS is expressed by fibroblasts, endothelial cells, and mesangial cells and has mitogenic regulatory activity, indicating a role in tumor suppression. During embryogenesis, SSeCKS is involved in controlling cytoskeletal structure and tissue architecture, forming the migratory process and cell migration (Gelman et al., 2000). The SSeCKS expression pattern is developmentally regulated in numerous cell types and tissues during perinatal growth, indicating a role in development and differentiation processes. In the nervous system of adult rats, SSeCKS is localized to central axonal collaterals of primary sensory neurons in the cerebellum, medulla, and sensory ganglia (including trigeminal ganglia) and in the dorsal horn at all spinal levels. In addition, SSeCKS is localized to C-fibers and is involved in nociception (Siegel et al., 2002). No prior studies have examined the involvement of SSeCKS in peripheral nerve injury; therefore, we examined the expression of SSeCKS in this condition, a complex process that remains poorly understood.Drs. Chen and Qin contributed equally to this work. *Correspondence to: Aiguo Shen, The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong, People's Republic of China, 226001. Fax: 86-513-85051999. E-mail: shen_aiguo@yahoo.com Abbreviations used: BSA = bovine serum albumin; PBS = phosphate-buffered saline; SSeCKS = src suppressed C kinase substrate; TBST = Tris-buffered saline with Tween; b 2 -M = b 2 -microglobulin; GAP43 = growth-associated protein 43.

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“…It is expressed at high levels in the developing nervous system (Biffo et al, 1990;Dani et al, 1991) and is induced after nerve injury (Benowitz et al, 1981;Skene and Willard 1981a,b;Verhaagen et al, 1988). A role of B-50/ in nerve fiber outgrowth is controversial and has been the subject of intense study.…”

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confidence: 99%

Directed expression of the growth-associated protein B-50/GAP-43 to olfactory neurons in transgenic mice results in changes in axon morphology and extraglomerular fiber growth

et al. 1995

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B-50/GAP-43, a neural growth-associated phosphoprotein, is thought to play a role in neuronal plasticity and nerve fiber formation since it is expressed at high levels in developing and regenerating neurons and in growth cones. Using a construct containing the coding sequence of B- 50/GAP-43 under the control of regulatory elements of the olfactory marker protein (OMP) gene, transgenic mice were generated to study the effect of directed expression of B-50/GAP-43 in a class of neurons that does not normally express B-50/GAP-43, namely, mature OMP-positive olfactory neurons. Olfactory neurons have a limited lifespan and are replaced throughout adulthood by new neurons that migrate into the upper compartment of the epithelium following their formation from stem cells in the basal portion of this neuroepithelium. Thus, the primary olfactory pathway is exquisitely suited to examine a role of B-50/GAP- 43 in neuronal migration, lifespan, and nerve fiber growth. We find that B-50/GAP-43 expression in adult olfactory neurons results in numerous primary olfactory axons with enlarged endings preferentially located at the rim of individual glomeruli. Furthermore, ectopic olfactory nerve fibers in between the juxtaglomerular neurons or in close approximation to blood vessels were frequently observed. This suggests that expression of B-50/GAP-43 in mature olfactory neurons alters their response to signals in the bulb. Other parameters examined, that is, migration and lifespan of olfactory neurons are normal in B-50/GAP-43 transgenic mice. These observations provide direct in vivo evidence for a role of B-50/GAP-43 in nerve fiber formation and in the determination of the morphology of axons.

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B‐50/GAP43 Expression Correlates with Process Outgrowth in the Embryonic Mouse Nervous System

Cited by 112 publications

References 63 publications

AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells

AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells

Spatiotemporal Expression of SSeCKS in Injured Rat Sciatic Nerve

Directed expression of the growth-associated protein B-50/GAP-43 to olfactory neurons in transgenic mice results in changes in axon morphology and extraglomerular fiber growth

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