No Nogo66- and NgR-Mediated Inhibition of Regenerating Axons in the Zebrafish Optic Nerve

Abdesselem, Houari; Shypitsyna, Aleksandra; Solis, Gonzalo P.; Bodrikov, Vsevolod; Stuermer, Claudia A. O.

doi:10.1523/jneurosci.3561-09.2009

Cited by 44 publications

(57 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, in zebrafish, CSPGs appear not to inhibit, but rather to guide optic nerve regeneration in zebrafish (Becker and Becker, 2002). Furthermore, orthologues of mammalian growth-inhibitory molecules and their receptors, like Nogo-family members, have been identified in fish (Abdesselem et al, 2009;Diekmann et al, 2005;Klinger et al, 2004). However, zebrafish NogoA lacks a specific domain that inhibits neurite outgrowth in mammals (Diekmann et al, 2005).…”

Section: Regeneration-permissive Features Of the Adult Zebrafish Telementioning

confidence: 99%

Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors

et al. 2011

View full text Add to dashboard Cite

SUMMARYSevere traumatic injury to the adult mammalian CNS leads to life-long loss of function. By contrast, several non-mammalian vertebrate species, including adult zebrafish, have a remarkable ability to regenerate injured organs, including the CNS. However, the cellular and molecular mechanisms that enable or prevent CNS regeneration are largely unknown. To study brain regeneration mechanisms in adult zebrafish, we developed a traumatic lesion assay, analyzed cellular reactions to injury and show that adult zebrafish can efficiently regenerate brain lesions and lack permanent glial scarring. Using Cre-loxP-based genetic lineage-tracing, we demonstrate that her4.1-positive ventricular radial glia progenitor cells react to injury, proliferate and generate neuroblasts that migrate to the lesion site. The newly generated neurons survive for more than 3 months, are decorated with synaptic contacts and express mature neuronal markers. Thus, regeneration after traumatic lesion of the adult zebrafish brain occurs efficiently from radial glia-type stem/progenitor cells.

show abstract

Section: Regeneration-permissive Features Of the Adult Zebrafish Telementioning

confidence: 99%

Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors

et al. 2011

View full text Add to dashboard Cite

show abstract

“…RTN1 belongs to a family of RTN proteins (RTN1-RTN4), which were first described in neuroendocrine cells to localize primarily to the ER membrane as ER-shaping proteins (8, 25). RTN4, also named Nogo, has previously been the only well-characterized member in the RTN family that has been shown to induce apoptosis, inhibit neuronal regeneration, and regulate protein trafficking (1,8,17). Our results showed that of the three RTN1 isoforms (RTN1A, RTN1B, and RTN1C), only RTN1A expression was increased in the kidney of both human and murine models of kidney disease and that the intensity of RTN1A staining in the tubulointerstitial compartment was correlated with the progression of DN.…”

mentioning

confidence: 99%

Knockdown of RTN1A attenuates ER stress and kidney injury in albumin overload-induced nephropathy

Xiao

Fan

Wang

et al. 2016

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Our previous studies have suggested a critical role of reticulon (RTN)1A in mediating endoplasmic reticulum (ER) stress in kidney cells of animal models and humans with kidney diseases. A large body of evidence suggests that proteinuria itself can cause tubular cell injury leading to the progression of kidney disease. In the present study, we determined whether RTN1A mediates proteinuria-induced tubular cell injury through increased ER stress. We found that incubation of HK2 cells with human serum albumin induced the expression of RTN1A and ER stress markers, whereas knockdown of RTN1A expression attenuated human serum albumin-induced ER stress and tubular cell apoptosis in vitro. In vivo, we found that tubular cell-specific RTN1 knockdown resulted in a significant attenuation of tubular cell ER stress, apoptosis, and renal fibrosis in a model of albumin overload nephropathy. Based on these findings, we conclude that RTN1A is a key mediator for proteinuria-induced tubular cell toxicity and renal fibrosis.reticulon-1; kidney disease; proteinuria; renal tubular cells; endoplasmic reticulum stress; apoptosis PROTEINURIA has been postulated to contribute to tubular cell injury and interstitial fibrosis (2,19). Studies have shown that patients with higher levels of proteinuria are at a greater risk of progression to end-stage renal disease (20,24). However, the underlying mechanisms of albumin-induced tubulointerstitial injury are not completely understood. Currently, there is no specific and effective therapy available to reduce the progression of chronic kidney disease (CKD) induced by proteinuria.Endoplasmic reticulum (ER) stress has been shown to contribute to the development and progression of CKD (9, 10). Cells respond to ER stress by activating the unfolded protein response (UPR), and glucose-regulated protein of 78 kDa (GRP78) serves as a central regulator of three main UPR sensors, namely, activating transcription factor (ATF)6, inositol-requiring enzyme (IRE)-1␣, and protein kinase RNA-like ER kinase (PERK), that initiate the UPR signaling pathway under ER stress. Increased expression of these ER stress markers was observed in the tubulointerstitial compartment of human kidneys with proteinuric kidney diseases such as diabetic nephropathy and human immunodeficiency virus-associated nephropathy (7,12).In a recent study (7), we found that increased expression of reticulon (RTN)1 was associated with the progression of CKD and inversely correlated with kidney function (as assessed by the estimated glomerular filatration rate) in patients with diabetic nephropathy (DN). RTN1 belongs to a family of RTN proteins (RTN1-RTN4), which were first described in neuroendocrine cells to localize primarily to the ER membrane as ER-shaping proteins (8, 25). RTN4, also named Nogo, has previously been the only well-characterized member in the RTN family that has been shown to induce apoptosis, inhibit neuronal regeneration, and regulate protein trafficking (1,8,17). Our results showed that of the three RTN1 isoforms (RTN1A, RT...

show abstract

“…It recognized the peptide against which it was raised and 210 kDa Nogo‐A in Western blots with lysates of cultured oligodendrocytes (Oertle et al, ) and binds to GST‐delta20 and GST‐M1–4 as well as to delta20 and M1–4 after cleavage of GST in our present study (Figure ). pAB IK964 is a polyclonal AB from a rabbit which was immunized with the His‐tagged Nogo‐66 peptide of zebrafish Rtn4a (Abdesselem et al, ; Pinzon‐Olejua et al, ; Claudia Stuermer Lab Universität Konstanz; Germany Cat# Rtn4a, RRID:AB_2636940). The specificity was shown in lysates of zebrafish embryos after injections of Rtn4a‐specific and control morpholinos, respectively, into the yolk at early stages of development, and by immunostainings at increasing developmental stages as well as in the adult optic nerve after lesion (Abdesselem et al, ).…”

Section: Methodsmentioning

confidence: 99%

Substrate properties of zebrafish Rtn4b/Nogo and axon regeneration in the zebrafish optic nerve

Bodrikov

Welte

Wiechers

et al. 2017

J of Comparative Neurology

View full text Add to dashboard Cite

This study explored why lesioned retinal ganglion cell (RGC) axons regenerate successfully in the zebrafish optic nerve despite the presence of Rtn4b, the homologue of the rat neurite growth inhibitor RTN4-A/Nogo-A. Rat Nogo-A and zebrafish Rtn4b possess characteristic motifs (M1-4) in the Nogo-A-specific region, which contains delta20, the most inhibitory region of rat Nogo-A. To determine whether zebrafish M1-4 is inhibitory as rat M1-4 and Nogo-A delta20, proteins were recombinantly expressed and used as substrates for zebrafish single cell RGCs, mouse hippocampal neurons and goldfish, zebrafish and chick retinal explants. When offered as homogenous substrates, neurites of hippocampal neurons and of zebrafish single cell RGCs were inhibited by zebrafish M1-4, rat M1-4, and Nogo-A delta20. Neurite length increased when zebrafish single cell RGCs were treated with receptor-type-specific antagonists and, respectively, with morpholinos (MO) against S1PR2 and S1PR5a-which represent candidate zebrafish Nogo-A receptors. In a stripe assay, however, where M1-4 lanes alternate with polylysine-(Plys)-only lanes, RGC axons from goldfish, zebrafish, and chick retinal explants avoided rat M1-4 but freely crossed zebrafish M1-4 lanes-suggesting that zebrafish M1-4 is growth permissive and less inhibitory than rat M1-4. Moreover, immunostainings and dot blots of optic nerve and myelin showed that expression of Rtn4b is very low in tissue and myelin at 3-5 days after lesion when axons regenerate. Thus, Rtn4b seems to represent no major obstacle for axon regeneration in vivo because it is less inhibitory for RGC axons from retina explants, and because of its low abundance.

show abstract

No Nogo66- and NgR-Mediated Inhibition of Regenerating Axons in the Zebrafish Optic Nerve

Cited by 44 publications

References 67 publications

Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors

Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors

Knockdown of RTN1A attenuates ER stress and kidney injury in albumin overload-induced nephropathy

Substrate properties of zebrafish Rtn4b/Nogo and axon regeneration in the zebrafish optic nerve

Contact Info

Product

Resources

About