{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:55:57Z","timestamp":1771037757518,"version":"3.50.1"},"reference-count":68,"publisher":"Society for Neuroscience","issue":"21","license":[{"start":{"date-parts":[[2001,5,1]],"date-time":"2001-05-01T00:00:00Z","timestamp":988675200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2000,11,1]]},"abstract":"<jats:p>In lower vertebrates, retinal ganglion cells (RGCs) can regenerate their axons and reestablish functional connections after optic nerve injury. We show here that in goldfish RGCs, the effects of several trophic factors converge on a purine-sensitive signaling mechanism that controls axonal outgrowth and the expression of multiple growth-associated proteins. In culture, goldfish RGCs regenerate their axons in response to two molecules secreted by optic nerve glia, axogenesis factor-1 (AF-1) and AF-2, along with ciliary neurotrophic factor. The purine analog 6-thioguanine (6-TG) blocked outgrowth induced by each of these factors. Previous studies in PC12 cells have shown that the effects of 6-TG on neurite outgrowth may be mediated via inhibition of a 47 kDa protein kinase. Growth factor-induced axogenesis in RGCs was accompanied by many of the molecular changes that characterize regenerative growth<jats:italic>in vivo<\/jats:italic>, e.g., increased expression of GAP-43 and certain cell surface glycoproteins. 6-TG inhibited all of these changes but not those associated with axotomy per se, e.g., induction of jun family transcription factors, nor did it affect cell survival. Additional studies using RGCs from transgenic zebrafish showed that expression of T\u03b1-1 tubulin is likewise stimulated by AF-1 and blocked by 6-TG. The purine nucleoside inosine had effects opposite to those of 6-TG. Inosine stimulated outgrowth and the characteristic pattern of molecular changes in RGCs and competitively reversed the inhibitory effects of 6-TG. We conclude that axon regeneration and the underlying program of gene expression in goldfish RGCs are mediated via a common, purine-sensitive pathway.<\/jats:p>","DOI":"10.1523\/jneurosci.20-21-08031.2000","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T15:10:31Z","timestamp":1522941031000},"page":"8031-8041","source":"Crossref","is-referenced-by-count":52,"title":["A Purine-Sensitive Pathway Regulates Multiple Genes Involved in Axon Regeneration in Goldfish Retinal Ganglion Cells"],"prefix":"10.1523","volume":"20","author":[{"given":"Barbara","family":"Petrausch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Tabibiazar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Roser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Jing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Goldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia A. O.","family":"Stuermer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Irwin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry I.","family":"Benowitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"393","published-online":{"date-parts":[[2000,11,1]]},"reference":[{"key":"2023041302464773000_20.21.8031.1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199807)23:3<257::AID-GLIA8>3.0.CO;2-1"},{"key":"2023041302464773000_20.21.8031.2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.721362.x"},{"key":"2023041302464773000_20.21.8031.3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1242\/dev.108.2.299","article-title":"The spatiotemporal distribution of N-CAM in the retinotectal pathway of adult goldfish detected by the monoclonal antibody D3.","volume":"108","author":"Bastmeyer","year":"1990","journal-title":"Development"},{"key":"2023041302464773000_20.21.8031.4","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.130.4.969"},{"key":"2023041302464773000_20.21.8031.5","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.3.3.363"},{"key":"2023041302464773000_20.21.8031.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.03-11-02153.1983"},{"key":"2023041302464773000_20.21.8031.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(96)10072-2"},{"key":"2023041302464773000_20.21.8031.8","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1523\/JNEUROSCI.01-03-00300.1981","article-title":"Specific changes in rapidly transported proteins during regeneration of the goldfish optic nerve.","volume":"1","author":"Benowitz","year":"1981","journal-title":"J Neurosci"},{"key":"2023041302464773000_20.21.8031.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.6194562"},{"key":"2023041302464773000_20.21.8031.10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.45.29626"},{"key":"2023041302464773000_20.21.8031.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.23.13486"},{"key":"2023041302464773000_20.21.8031.12","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1002\/j.1460-2075.1986.tb04667.x","article-title":"Regulation of protein kinase activities in PC12 pheochromocytoma cells.","volume":"5","author":"Blenis","year":"1986","journal-title":"EMBO J"},{"key":"2023041302464773000_20.21.8031.13","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19980515)52:4<405::AID-JNR4>3.0.CO;2-D"},{"key":"2023041302464773000_20.21.8031.14","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1471-4159.1978.tb12462.x","article-title":"RNA metabolism in the goldfish retina during optic nerve regeneration.","volume":"31","author":"Burrell","year":"1978","journal-title":"J Neurochem"},{"key":"2023041302464773000_20.21.8031.15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0169-328X(89)90016-8","article-title":"Partial purification and characterization of a neurite-promoting factor secreted by the regenerating goldfish optic nerve.","volume":"5","author":"Caday","year":"1989","journal-title":"Mol Brain Res"},{"key":"2023041302464773000_20.21.8031.16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.34.20713"},{"key":"2023041302464773000_20.21.8031.17","first-page":"760","article-title":"CNTF, not other trophic factors, promotes axonal regeneration of axotomized retinal ganglion cells in adult hamsters.","volume":"40","author":"Cui","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2023041302464773000_20.21.8031.18","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19970113)377:2<286::AID-CNE9>3.0.CO;2-#"},{"key":"2023041302464773000_20.21.8031.19","doi-asserted-by":"crossref","first-page":"6494","DOI":"10.1016\/S0021-9258(18)43767-2","article-title":"Biosynthesis and intra-axonal transport of proteins during neuronal regeneration.","volume":"255","author":"Giulian","year":"1980","journal-title":"J Biol Chem"},{"key":"2023041302464773000_20.21.8031.20","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90175-D"},{"key":"2023041302464773000_20.21.8031.21","doi-asserted-by":"crossref","unstructured":"Grafstein B (1986) The retina as a regenerating organ. in The retina: a model for cell biology studies, Pt II, eds Adler R Farber DB (Academic, New York), pp 275\u2013335.","DOI":"10.1016\/B978-0-12-044276-8.50013-8"},{"key":"2023041302464773000_20.21.8031.22","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-05-01479.1990"},{"key":"2023041302464773000_20.21.8031.23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb04955.x"},{"key":"2023041302464773000_20.21.8031.24","doi-asserted-by":"publisher","DOI":"10.1007\/BF00965529"},{"key":"2023041302464773000_20.21.8031.25","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480240410"},{"key":"2023041302464773000_20.21.8031.26","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(19981115)37:3<429::AID-NEU8>3.0.CO;2-N"},{"key":"2023041302464773000_20.21.8031.27","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480250109"},{"key":"2023041302464773000_20.21.8031.28","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(65)90128-7"},{"key":"2023041302464773000_20.21.8031.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00546-6"},{"key":"2023041302464773000_20.21.8031.30","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202524"},{"key":"2023041302464773000_20.21.8031.31","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.5.2451"},{"key":"2023041302464773000_20.21.8031.32","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-15-05692.1998"},{"key":"2023041302464773000_20.21.8031.33","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(199601)29:1<65::AID-NEU5>3.0.CO;2-5"},{"key":"2023041302464773000_20.21.8031.34","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(91)90089-T"},{"key":"2023041302464773000_20.21.8031.35","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(199812)37:4<502::AID-NEU2>3.0.CO;2-S"},{"key":"2023041302464773000_20.21.8031.36","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.2.339"},{"key":"2023041302464773000_20.21.8031.37","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1523\/JNEUROSCI.10-01-00256.1990","article-title":"GAP-43 in growth cones is associated with areas of membrane that are tightly bound to substrate and is a component of a membrane skeleton subcellular fraction.","volume":"10","author":"Meiri","year":"1990","journal-title":"J Neurosci"},{"key":"2023041302464773000_20.21.8031.38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-24-10429.1998"},{"key":"2023041302464773000_20.21.8031.39","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90695-J"},{"key":"2023041302464773000_20.21.8031.40","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90172-8"},{"key":"2023041302464773000_20.21.8031.41","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901680202"},{"key":"2023041302464773000_20.21.8031.42","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(71)90325-8"},{"key":"2023041302464773000_20.21.8031.43","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-09-03363.1998"},{"key":"2023041302464773000_20.21.8031.44","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.117.4.863"},{"key":"2023041302464773000_20.21.8031.45","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.07-03-00792.1987"},{"key":"2023041302464773000_20.21.8031.46","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(80)91039-2"},{"key":"2023041302464773000_20.21.8031.47","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1471-4159.1990.tb01890.x","article-title":"Multiple pathways of N-kinase activation in PC12 cells.","volume":"54","author":"Rowland-Gagne","year":"1990","journal-title":"J Neurochem"},{"key":"2023041302464773000_20.21.8031.48","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1242\/dev.124.2.577","article-title":"Reggie-1 and Reggie-2, two cell surface proteins expressed by retinal ganglion cells during axon regeneration.","volume":"124","author":"Schulte","year":"1997","journal-title":"Development"},{"key":"2023041302464773000_20.21.8031.49","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-08-05514.1995"},{"key":"2023041302464773000_20.21.8031.50","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00605-2"},{"key":"2023041302464773000_20.21.8031.51","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(81)90535-7"},{"key":"2023041302464773000_20.21.8031.52","doi-asserted-by":"publisher","DOI":"10.1126\/science.3983646"},{"key":"2023041302464773000_20.21.8031.53","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.89.1.86"},{"key":"2023041302464773000_20.21.8031.54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.50.4.703"},{"key":"2023041302464773000_20.21.8031.55","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-24-10502.1998"},{"key":"2023041302464773000_20.21.8031.56","doi-asserted-by":"publisher","DOI":"10.1126\/science.8272873"},{"key":"2023041302464773000_20.21.8031.57","doi-asserted-by":"publisher","DOI":"10.1038\/342920a0"},{"key":"2023041302464773000_20.21.8031.58","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.115.2.447"},{"key":"2023041302464773000_20.21.8031.59","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90495-6"},{"key":"2023041302464773000_20.21.8031.60","unstructured":"Stuermer CAO, Plattner H, Lang DM, Kirsch F (2000) Exploring the function of reggie-1 and -2, components of non-caveolar plasma membrane microdomains. Eur J Neurosci, in press."},{"key":"2023041302464773000_20.21.8031.61","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(06)00298-3"},{"key":"2023041302464773000_20.21.8031.62","doi-asserted-by":"publisher","DOI":"10.1042\/bj2880351"},{"key":"2023041302464773000_20.21.8031.63","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-11-03581.1991"},{"key":"2023041302464773000_20.21.8031.64","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb09774.x"},{"key":"2023041302464773000_20.21.8031.65","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.5.2395"},{"key":"2023041302464773000_20.21.8031.66","first-page":"221","article-title":"Cell signalling and CAM-mediated neurite outgrowth.","volume":"52","author":"Walsh","year":"1997","journal-title":"Soc Gen Physiol Ser"},{"key":"2023041302464773000_20.21.8031.67","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1997.0603"},{"key":"2023041302464773000_20.21.8031.68","doi-asserted-by":"publisher","DOI":"10.1126\/science.7701324"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.20-21-08031.2000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T13:39:16Z","timestamp":1681393156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.20-21-08031.2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,11,1]]},"references-count":68,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2000,11,1]]},"published-print":{"date-parts":[[2000,11,1]]}},"alternative-id":["10.1523\/JNEUROSCI.20-21-08031.2000"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.20-21-08031.2000","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,11,1]]}}}