{"doi":"10.1242/dev.013995","title":"Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in<i>C. elegans</i>","abstract":"<jats:p>The molecular and cellular mechanisms that allow adult-stage neurons to regenerate following damage are poorly understood. Recently, axons of motoneurons and mechanosensory neurons in adult C. elegans were found to regrow after being snipped by femtosecond laser ablation. Here, we explore the molecular determinants of adult-stage axon regeneration using the AVM mechanosensory neurons. The first step in AVM axon development is a pioneer axonal projection from the cell body to the ventral nerve cord. We show that regeneration of the AVM axon to the ventral nerve cord lacks the deterministic precision of initial axon development, requiring competition and pruning of unwanted axon branches. Nevertheless, axons of injured AVM neurons regrow to the ventral nerve cord with over 60% reliability in adult animals. In addition, in contrast to initial development, axon guidance during regeneration becomes heavily dependent on cytoplasmic protein MIG-10/Lamellipodin but independent of UNC-129/TGF-β repellent and UNC-40/DCC receptor, and axon growth during regeneration becomes heavily dependent on UNC-34/Ena and CED-10/Rac actin regulators. Thus, C. elegans may be used as a genetic system to characterize novel cellular and molecular mechanisms underlying adult-stage nervous system regeneration.</jats:p>","journal":"Development","year":2008,"id":647858,"datarank":3.9181611894472064,"base_score":4.59511985013459,"endowment":4.59511985013459,"self_citation_contribution":0.6892679775201885,"citation_network_contribution":3.228893211927018,"self_endowment_contribution":0.6892679775201885,"citer_contribution":3.228893211927018,"corpus_percentile":null,"corpus_rank":null,"citation_count":98,"citer_count":82,"citers_with_citation_signal":77,"citers_with_endowment":77,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1688079,"name":"Faustine Antoine","orcid":null,"position":1,"is_corresponding":false},{"id":1688080,"name":"Chiou-Fen Chuang","orcid":null,"position":2,"is_corresponding":false},{"id":164494,"name":"Aravinthan D. T. Samuel","orcid":null,"position":3,"is_corresponding":false},{"id":821431,"name":"Chieh Chang","orcid":"0000-0003-3476-2751","position":4,"is_corresponding":false},{"id":443908,"name":"Christopher V. Gabel","orcid":"0000-0002-2763-3938","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in<i>C. elegans</i>","abstract":"<jats:p>The molecular and cellular mechanisms that allow adult-stage neurons to regenerate following damage are poorly understood. Recently, axons of motoneurons and mechanosensory neurons in adult C. elegans were found to regrow after being snipped by femtosecond laser ablation. Here, we explore the molecular determinants of adult-stage axon regeneration using the AVM mechanosensory neurons. The first step in AVM axon development is a pioneer axonal projection from the cell body to the ventral nerve cord. We show that regeneration of the AVM axon to the ventral nerve cord lacks the deterministic precision of initial axon development, requiring competition and pruning of unwanted axon branches. Nevertheless, axons of injured AVM neurons regrow to the ventral nerve cord with over 60% reliability in adult animals. In addition, in contrast to initial development, axon guidance during regeneration becomes heavily dependent on cytoplasmic protein MIG-10/Lamellipodin but independent of UNC-129/TGF-β repellent and UNC-40/DCC receptor, and axon growth during regeneration becomes heavily dependent on UNC-34/Ena and CED-10/Rac actin regulators. Thus, C. elegans may be used as a genetic system to characterize novel cellular and molecular mechanisms underlying adult-stage nervous system regeneration.</jats:p>","is_dataset_classified":null,"base_score":4.59511985013459,"endowment":4.59511985013459,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18296652","pmcid":null,"openalex_id":"https://openalex.org/W2023904562","authors":[],"funders":[],"total_grants":0,"fwci":2.9425,"citation_percentile":0.91042345,"influential_citations":0,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":9},{"year":2014,"count":7},{"year":2015,"count":2},{"year":2016,"count":8},{"year":2017,"count":9},{"year":2018,"count":4},{"year":2019,"count":3},{"year":2020,"count":5},{"year":2021,"count":4},{"year":2022,"count":2},{"year":2023,"count":2},{"year":2024,"count":2},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://journals.biologists.com/dev/article-pdf/135/6/1129/1537728/1129.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/dev.013995","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18296652","host_type":"repository"}],"fields_of_study":["Genetics, Aging, and Longevity in Model Organisms","3D Printing in Biomedical Research","Sirtuins and Resveratrol in Medicine","Animals","Animals, Genetically Modified","Axons","Caenorhabditis elegans","Caenorhabditis elegans Proteins","Genes, Helminth","Models, Neurological","Motor Neurons","Mutation","Nerve Regeneration","Nerve Tissue Proteins","Neurons","rac GTP-Binding Proteins"],"mesh_terms":["Animals","Axons","Models, Neurological","Motor Neurons","Mutation","Nerve Regeneration","Nerve Tissue Proteins","Neurons","Caenorhabditis elegans","Genes, Helminth","rac GTP-Binding Proteins","Caenorhabditis elegans Proteins","Animals, Genetically Modified"],"keywords":["Axon","Biology","Regeneration (biology)","Axon guidance","Neuroscience","Exocyst","Ventral nerve cord","Axon hillock","Growth cone","Nervous system","Cell biology","Anatomy","Protein subunit","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T01:57:54.972985Z","pmid":null,"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":[]}