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This failure is generally attributed to an insufficient intrinsic regenerative capacity, the extrinsic inhibitory environment, and RGC death. Here, we show that a chemoattractive CXCL12\/CXCR4-dependent mechanism entraps growth-stimulated axons at the lesion site, thereby limiting axon extension in the nerve. Accordingly, specific depletion of either CXCR4 or CXCL12 in growth-stimulated RGCs releases entrapped axons and markedly enhances nerve regeneration at long distances. Thus, active CXCL12\/CXCR4-mediated attraction to the injury site represents a mechanism preventing central nervous system (CNS) axon regeneration. Moreover, treatments targeting CXCL12\/CXCR4 signaling may be promising approaches to improve CNS repair.<\/jats:p>","DOI":"10.1073\/pnas.2016409118","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T15:35:49Z","timestamp":1621438549000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":24,"title":["CXCR4\/CXCL12-mediated entrapment of axons at the injury site compromises optic nerve regeneration"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5694-3097","authenticated-orcid":false,"given":"Alexander M.","family":"Hilla","sequence":"first","affiliation":[{"name":"Department of Cell Physiology, Faculty of Biology and Biotechnology, Ruhr University, 44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie","family":"Baehr","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology, Faculty of Biology and Biotechnology, Ruhr University, 44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Leibinger","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology, Faculty of Biology and Biotechnology, Ruhr University, 44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9278-6394","authenticated-orcid":false,"given":"Anastasia","family":"Andreadaki","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology, Faculty of Biology and Biotechnology, Ruhr University, 44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1816-3014","authenticated-orcid":false,"given":"Dietmar","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology, Faculty of Biology and Biotechnology, Ruhr University, 44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00602-5"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1302-7"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2012.06.005"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.11.006"},{"key":"e_1_3_4_5_2","first-page":"3943","article-title":"Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture","volume":"41","author":"Fischer D.","year":"2000","unstructured":"D. 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