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However, the molecular mechanisms coordinating proper axonal extension and turning are poorly understood. Here, metastasis suppressor 1 (Mtss1), a membrane protrusion protein, ensured axonal extension while sensitizing axons to the Semaphorin 3E (Sema3E)-Plexin-D1 repulsive cue. Sema3E-Plexin-D1 signaling enhanced Mtss1 expression in projecting striatonigral neurons. Mtss1 localized to the neurite axonal side and regulated neurite outgrowth in cultured neurons. Mtss1 also aided Plexin-D1 trafficking to the growth cone, where it signaled a repulsive cue to Sema3E. Mtss1 ablation reduced neurite extension and growth cone collapse in cultured neurons.\n                    <jats:italic>Mtss1<\/jats:italic>\n                    -knockout mice exhibited fewer striatonigral projections and irregular axonal routes, and these defects were recapitulated in\n                    <jats:italic>Plxnd1<\/jats:italic>\n                    - or\n                    <jats:italic>Sema3e<\/jats:italic>\n                    -knockout mice. These findings demonstrate that repulsive axon guidance activates an exquisite autoregulatory program coordinating both axonal extension and steering during neuronal pathfinding.\n                  <\/jats:p>","DOI":"10.7554\/elife.96891","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T06:15:06Z","timestamp":1711347306000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.96891","source":"Crossref","is-referenced-by-count":8,"title":["Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5043-0293","authenticated-orcid":true,"given":"Namsuk","family":"Kim","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055zd7d59","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurovascular Unit Research Group, Korea Brain Research Institute","place":["Daegu, Republic of 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