{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:10:44Z","timestamp":1788487844020,"version":"build-2803163510"},"reference-count":0,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RO1 NS114219"],"award-info":[{"award-number":["RO1 NS114219"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RO1 NS114219"],"award-info":[{"award-number":["RO1 NS114219"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30 GM145646; P20 GM103650"],"award-info":[{"award-number":["P30 GM145646; P20 GM103650"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>SLIT2 is a secreted protein that repels axons from the CNS midline. Full-length SLIT2 (SLIT2-FL) is proteolytically cleaved into two fragments, SLIT2-N and SLIT2-C. SLIT2-FL and SLIT2-N have opposing biological effects on cultured dorsal root ganglion (DRG) axons. This study identified SLIT2 cleavage mechanisms and functional significance for DRG axon guidance. The Tolloid related protease TLL1 cleaved SLIT2 in cultured cells, with TLL1 requiring activation by furin\/prohormone convertases. We used CRISPR editing in mice to produce a Slit2DTLS allele lacking the TLL1 cleavage site. Slit2DTLS embryos retained dorsal repulsion of DRG axons, in contrast to DRG midline invasion in Slit2 knockouts. However, DRG axons in Slit2 knockouts and Slit2DTLS mutants showed reduced fasciculation of rootlets and longitudinal DRG projections. In vitro, SLIT2-N promoted fasciculation of DRG axons. These results suggest that proteolytic cleavage generates additional SLIT2 biological functions for organizing DRG central axon projections.<\/jats:p>","DOI":"10.1242\/dev.205124","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:51:40Z","timestamp":1770036700000},"source":"Crossref","is-referenced-by-count":1,"title":["SLIT2 repellent is cleaved by TLL1 protease and promotes sensory axon fasciculation"],"prefix":"10.1242","author":[{"given":"Lauren E.","family":"Jones","sequence":"first","affiliation":[{"name":"1 Department of Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4196-168X","authenticated-orcid":false,"given":"Riley","family":"Kellermeyer","sequence":"additional","affiliation":[{"name":"1 Department of Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ria","family":"Anand","sequence":"additional","affiliation":[{"name":"1 Department of Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayden","family":"Watson","sequence":"additional","affiliation":[{"name":"1 Department of Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Smith","sequence":"additional","affiliation":[{"name":"1 Department of Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1570-7574","authenticated-orcid":false,"given":"Xieyi","family":"Huang","sequence":"additional","affiliation":[{"name":"1 Department of Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuqing","family":"Wang","sequence":"additional","affiliation":[{"name":"2 Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yan","sequence":"additional","affiliation":[{"name":"2 Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"3 Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9148-6194","authenticated-orcid":false,"given":"Cynthia C.","family":"Mastick","sequence":"additional","affiliation":[{"name":"1 Department of Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7190-4208","authenticated-orcid":false,"given":"Thomas","family":"Kidd","sequence":"additional","affiliation":[{"name":"1 Department of Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant S.","family":"Mastick","sequence":"additional","affiliation":[{"name":"1 Department of Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,2,2]]},"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.205124\/3683180\/dev205124.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.205124\/3683180\/dev205124.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:51:41Z","timestamp":1770036701000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/doi\/10.1242\/dev.205124\/370551\/SLIT2-repellent-is-cleaved-by-TLL1-protease-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1242\/dev.205124","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]},"article-number":"dev.205124"}}