{"doi":"10.1242/dev.196055","title":"Proteolytic cleavage of Slit by the Tolkin protease converts an axon repulsion cue to an axon growth cue <i>in vivo</i>","abstract":"Slit is a secreted protein that has a canonical function of repelling growing axons from the CNS midline. The full-length Slit (Slit-FL) is cleaved into Slit-N and Slit-C fragments, which have potentially distinct functions via different receptors. Here we report that the BMP-1/Tolloid family metalloprotease, Tolkin (Tok), is responsible for Slit proteolysis in vivo and in vitro. In tok mutants lacking Slit cleavage, midline repulsion of axons occurs normally, confirming that Slit-FL is sufficient to repel axons. However, longitudinal axon guidance is highly disrupted in tok mutants and can be rescued by midline expression of Slit-N, suggesting that Slit is the primary substrate for Tok in the embryonic CNS. Transgenic restoration of Slit-N or Slit-C does repel axons in Slit-null animals. Slit-FL and Slit-N are both biologically active cues with distinct axon guidance functions in vivo. Slit signaling is used in diverse biological processes, thus differentiating between Slit-FL and Slit fragments will be essential for evaluating Slit function in broader contexts.","journal":"Development","year":2020,"id":78228,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":408154,"name":"Leah M. Heydman","orcid":null,"position":1,"is_corresponding":false},{"id":407107,"name":"Taylor Gillis","orcid":"0000-0003-0195-6496","position":2,"is_corresponding":false},{"id":407108,"name":"Grant S. Mastick","orcid":"0000-0002-9148-6194","position":3,"is_corresponding":false},{"id":407109,"name":"Minmin Song","orcid":"0000-0002-3519-9983","position":4,"is_corresponding":false},{"id":407110,"name":"Thomas Kidd","orcid":"0000-0001-7190-4208","position":5,"is_corresponding":false},{"id":407106,"name":"Riley Kellermeyer","orcid":"0000-0002-4196-168X","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T21:49:40.769098Z","pmid":"32994163","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}