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

Welte, Cornelia; Engel, Sarah; Stürmer, Claudia

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

Dateien

Welte_0-287224.pdfGröße: 2.49 MBDownloads: 342

Datum

2015

Publikationstyp

Zeitschriftenartikel

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Neural Development. 2015, 10, 6. eISSN 1749-8104. Available under: doi: 10.1186/s13064-015-0034-x

Zusammenfassung

Background

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.

Results

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.

Conclusions

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.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

Optic nerve lesion, Axon regeneration, Rtn4b upregulation, ER, Morpholino downregulation, Retinal ganglion cells, Neuron-intrinsic determinants, Nogo-A/RTN4A

Zitieren

ISO 690

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

BibTex

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

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