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Upregulation of the zebrafish Nogo-A homologue, Rtn4b, in retinal ganglion cells is functionally involved in axon regeneration

Upregulation of the zebrafish Nogo-A homologue, Rtn4b, in retinal ganglion cells is functionally involved in axon regeneration

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Prüfsumme: MD5:6e0c9f84b5c7043343f7e90172048052

WELTE, Cornelia, Sarah ENGEL, Claudia A. O. STUERMER, 2015. Upregulation of the zebrafish Nogo-A homologue, Rtn4b, in retinal ganglion cells is functionally involved in axon regeneration. In: Neural Development. 10, 6. eISSN 1749-8104. Available under: doi: 10.1186/s13064-015-0034-x

@article{Welte2015Upreg-31123, title={Upregulation of the zebrafish Nogo-A homologue, Rtn4b, in retinal ganglion cells is functionally involved in axon regeneration}, year={2015}, doi={10.1186/s13064-015-0034-x}, volume={10}, journal={Neural Development}, author={Welte, Cornelia and Engel, Sarah and Stuermer, Claudia A. O.}, note={Article Number: 6} }

2015-06-10T07:50:54Z Upregulation of the zebrafish Nogo-A homologue, Rtn4b, in retinal ganglion cells is functionally involved in axon regeneration 2015 Background<br /><br />In contrast to mammals, zebrafish successfully regenerate retinal ganglion cell (RGC) axons after optic nerve section (ONS). This difference is explained on the one hand by neurite growth inhibitors in mammals (including Nogo-A), as opposed to growth-promoting glial cells in the fish visual pathway, and on the other hand by the neuron-intrinsic properties allowing the upregulation of growth-associated proteins in fish RGCs but not in mammals.<br /><br />Results<br /><br />Here, we report that Rtn4b, the zebrafish homologue of mammalian Nogo-A/RTN4-A, is upregulated in axotomized zebrafish RGCs and is primarily associated with the endoplasmic reticulum (ER). Rtn4b functions as a neuron-intrinsic determinant for axon regeneration, as was shown by downregulating Rtn4b through retrogradely transported morpholinos (MOs), applied to the optic nerve at the time of ONS. MO1 and MO2 reduced the number of axons from retina explants in a concentration-dependent manner. With MO1, the reduction was 55% (70 μM MO1) and 74% (140 μM MO1), respectively, with MO2: 59% (70 μM MO2) and 73% (140 μM MO2), respectively (compared to the control MO-treated side). Moreover, regenerating axons 7d after ONS and MO1 or MO2 application were labeled by Alexa488, applied distal to the first lesion. The number of Alexa488 labeled RGCs, containing the Rtn4b MO1 or MO2, was reduced by 54% and 62%, respectively, over control MO.<br /><br />Conclusions<br /><br />Thus, Rtn4b is an important neuron-intrinsic component and required for the success of axon regeneration in the zebrafish visual system. The spontaneous lesion-induced upregulation of Rtn4b in fish correlates with an increase in ER, soma size, biosynthetic activity, and thus growth and predicts that mammalian neurons require the same upregulation in order to successfully regenerate RGC axons. eng Engel, Sarah 2015-06-10T07:50:54Z Welte, Cornelia Welte, Cornelia Stuermer, Claudia A. O. Engel, Sarah Stuermer, Claudia A. O.

Dateiabrufe seit 10.06.2015 (Informationen über die Zugriffsstatistik)

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