{"doi":"10.1523/eneuro.0324-19.2020","title":"Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice","abstract":"<jats:p>Doublecortin (DCX)-like (DCL) is a microtubule (MT)-associated protein (MAP) that is highly homologous to DCX and is crucially involved in embryonic neurogenesis. Here, we have investigated the<jats:italic>in vivo</jats:italic>role of DCL in adult hippocampal neurogenesis by generating transgenic mice producing inducible shRNA molecules that specifically target DCL but no other splice variants produced by the DCLK gene. DCL knock-down (DCL-KD) resulted in a significant increase in the number of proliferating BrdU+ cells in the subgranular zone (SGZ) 1 d after BrdU administration. However, the number of surviving newborn adult NeuN+/BrdU+ neurons are significantly decreased when inspected four weeks after BrdU administration suggesting a blockade of neuronal differentiation after DCL-KD. In line with this, we observed an increase in the number of proliferating cells, but a significant decrease in postmitotic DCX+ cells that are characterized by long dendrites spanning all dentate gyrus layers. Behavioral analysis showed that DCL-KD strongly extended the escape latency of mice on the circular hole board (CHB) but did not affect other aspects of this behavioral task. Together, our results indicate a function for DCL in adult neurogenesis and in the motivation to escape from an aversive environment. In contrast to DCX, its pivotal role in the maturation of postmitotic neuronal progenitor cells (NPCs) marks DCL as a genuine adult neurogenesis indicator in the hippocampus.</jats:p>","journal":"eneuro","year":2020,"id":662777,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1208556,"name":"Erik W. van Zwet","orcid":"0000-0001-5537-3179","position":1,"is_corresponding":false},{"id":113919,"name":"Erno Vreugdenhil","orcid":null,"position":2,"is_corresponding":false},{"id":1730321,"name":"Dirk-Jan Saaltink","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice","abstract":"<jats:p>Doublecortin (DCX)-like (DCL) is a microtubule (MT)-associated protein (MAP) that is highly homologous to DCX and is crucially involved in embryonic neurogenesis. Here, we have investigated the<jats:italic>in vivo</jats:italic>role of DCL in adult hippocampal neurogenesis by generating transgenic mice producing inducible shRNA molecules that specifically target DCL but no other splice variants produced by the DCLK gene. DCL knock-down (DCL-KD) resulted in a significant increase in the number of proliferating BrdU+ cells in the subgranular zone (SGZ) 1 d after BrdU administration. However, the number of surviving newborn adult NeuN+/BrdU+ neurons are significantly decreased when inspected four weeks after BrdU administration suggesting a blockade of neuronal differentiation after DCL-KD. In line with this, we observed an increase in the number of proliferating cells, but a significant decrease in postmitotic DCX+ cells that are characterized by long dendrites spanning all dentate gyrus layers. Behavioral analysis showed that DCL-KD strongly extended the escape latency of mice on the circular hole board (CHB) but did not affect other aspects of this behavioral task. Together, our results indicate a function for DCL in adult neurogenesis and in the motivation to escape from an aversive environment. In contrast to DCX, its pivotal role in the maturation of postmitotic neuronal progenitor cells (NPCs) marks DCL as a genuine adult neurogenesis indicator in the hippocampus.</jats:p>","is_dataset_classified":null,"base_score":2.772588722239781,"endowment":2.772588722239781,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32994174","pmcid":"PMC7568604","openalex_id":"https://openalex.org/W3091004710","authors":[],"funders":[{"funder_name":"Top Institute Pharma, The Netherlands","grant_id":"T5-210","title":null}],"total_grants":1,"fwci":1.1671,"citation_percentile":0.74924925,"influential_citations":0,"citation_trend":[{"year":2020,"count":1},{"year":2021,"count":5},{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.eneuro.org/content/eneuro/7/5/ENEURO.0324-19.2020.full.pdf","host_type":"journal"},{"url":"https://www.eneuro.org/content/eneuro/7/5/ENEURO.0324-19.2020.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1523/ENEURO.0324-19.2020","host_type":"publisher"},{"url":"https://doi.org/10.1523/eneuro.0324-19.2020","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32994174","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7568604","host_type":"repository"},{"url":"http://hdl.handle.net/1887/3185032","host_type":"repository"},{"url":"https://www.eneuro.org/content/7/5/ENEURO.0324-19.2020","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7568604","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7568604?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Neurogenesis and neuroplasticity mechanisms","Axon Guidance and Neuronal Signaling","MicroRNA in disease regulation","Animals","Cell Proliferation","Dentate Gyrus","Doublecortin Domain Proteins","Doublecortin Protein","Escape Reaction","Hippocampus","Male","Mice","Mice, Transgenic","Microtubule-Associated Proteins","Motivation","Neurogenesis","Neuropeptides"],"mesh_terms":["Doublecortin Domain Proteins","Doublecortin Protein","Animals","Escape Reaction","Hippocampus","Male","Mice, Transgenic","Microtubule-Associated Proteins","Motivation","Neuropeptides","Dentate Gyrus","Cell Proliferation","Mice","Neurogenesis"],"keywords":["Neurogenesis","Doublecortin","Dentate gyrus","Subgranular zone","NeuN","Hippocampal formation","Neuroscience","Biology","Cell biology","Bromodeoxyuridine","Progenitor cell","Hippocampus","Stem cell","Immunology","Subventricular zone","Immunohistochemistry","Cognition","RNA interference","Dclk1"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T17:25:10.115010Z","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":[]}