Nogo-A does not inhibit retinal axon regeneration in the lizard Gallotia galloti.
The myelin-associated protein Nogo-A contributes to the failure of axon regeneration in the mammalian central nervous system (CNS). Inhibition of axon growth by Nogo-A is mediated by the Nogo-66 receptor (NgR). Nonmammalian vertebrates, however, are capable of spontaneous CNS axon regeneration, and we have shown that retinal ganglion cell (RGC) axons regenerate in the lizard Gallotia galloti. Using immunohistochemistry, we observed spatiotemporal regulation of Nogo-A and NgR in cell bodies and axons of RGCs during ontogeny. In the adult lizard, expression of Nogo-A was associated with myelinated axon tracts and upregulated in oligodendrocytes during RGC axon regeneration. NgR became upregulated in RGCs following optic nerve injury. In in vitro studies, Nogo-A-Fc failed to inhibit growth of lizard RGC axons. The inhibitor of protein kinase A (pkA) activity KT5720 blocked growth of lizard RGC axons on substrates of Nogo-A-Fc, but not laminin. On patterned substrates of Nogo-A-Fc, KT5720 caused restriction of axon growth to areas devoid of Nogo-A-Fc. Levels of cyclic adenosine monophosphate (cAMP) were elevated over sustained periods in lizard RGCs following optic nerve lesion. We conclude that Nogo-A and NgR are expressed in a mammalian-like pattern and are upregulated following optic nerve injury, but the presence of Nogo-A does not inhibit RGC axon regeneration in the lizard visual pathway. The results of outgrowth assays suggest that outgrowth-promoting substrates and activation of the cAMP/pkA signaling pathway play a key role in spontaneous lizard retinal axon regeneration in the presence of Nogo-A. Restriction of axon growth by patterned Nogo-A-Fc substrates suggests that Nogo-A may contribute to axon guidance in the lizard visual system. J. Comp. Neurol. 525:936-954, 2017. © 2016 Wiley Periodicals, Inc.
Division of Physiological Sciences, Department of Human Biology, University of Cape Town, Observatory, 7925, South Africa.
Dirk M
DM
Lang
Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, 35016 Las Palmas, Canary Islands, Spain.
Maria Del Mar
MD
Romero-Alemán
Division of Physiological Sciences, Department of Human Biology, University of Cape Town, Observatory, 7925, South Africa.
Bryony
B
Dobson
Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, 35016 Las Palmas, Canary Islands, Spain.
Elena
E
Santos
Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, 35016 Las Palmas, Canary Islands, Spain.
Maximina
M
Monzón-Mayor
D000818:Animals; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008116:Lizards; D009416:Nerve Regeneration / Q000502:physiology*; D000070798:Nogo Proteins / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D059008:Time-Lapse Imaging
D000070798:Nogo Proteins
AB_2314901; RRID: AB_10000211; RRID: AB_11211656; RRID: AB_1620281; RRID: AB_257899; RRID: AB_2619717; RRID: AB_357520; RRID: AB_477010; RRID: SCR_002078; RRID: SCR_002677; axon regeneration; development; neurite growth inhibitor; optic pathway; reptile