{"doi":"10.1007/s12035-021-02584-7","title":"Function of Oncogene Mycn in Adult Neurogenesis and Oligodendrogenesis","abstract":"<jats:title>Abstract</jats:title><jats:p>Human <jats:italic>MYCN</jats:italic> is an oncogene amplified in neuroblastoma and many other tumors. Both human <jats:italic>MYCN</jats:italic> and mouse <jats:italic>Mycn</jats:italic> genes are important in embryonic brain development, but their functions in adult healthy nerve system are completely unknown. Here, with <jats:italic>Mycn</jats:italic>-eGFP mice and quantitative RT-PCR, we found that <jats:italic>Mycn</jats:italic> was expressed in specific brain regions of young adult mice, including subventricular zone (SVZ), subgranular zone (SGZ), olfactory bulb (OB), subcallosal zone (SCZ), and corpus callosum (CC). With immunohistochemistry (IHC), we found that many <jats:italic>Mycn</jats:italic>-expressing cells expressed neuroblast marker doublecortin (DCX) and proliferation marker Ki67. With <jats:italic>Dcx-creER</jats:italic> and <jats:italic>Mki67-creER</jats:italic> mouse lines, we fate mapped <jats:italic>Dcx</jats:italic>-expressing neuroblasts and <jats:italic>Mki67</jats:italic>-expressing proliferation cells, along with deleting <jats:italic>Mycn</jats:italic> from these cells in adult mice. We found that knocking out <jats:italic>Mycn</jats:italic> from adult neuroblasts or proliferating cells significantly reduced cells in proliferation in SVZ, SGZ, OB, SCZ, and CC. We also demonstrated that the <jats:italic>Mycn</jats:italic>-deficient neuroblasts in SGZ matured quicker than wild-type neuroblasts, and that <jats:italic>Mycn</jats:italic>-deficient proliferating cells were more likely to survive in SVZ, SGZ, OB, SCZ, and CC compared to wild type. Thus, our results demonstrate that, in addition to causing tumors in the nervous system, oncogene <jats:italic>Mycn</jats:italic> has a crucial function in neurogenesis and oligodendrogenesis in adult healthy brain.</jats:p>","journal":"Molecular Neurobiology","year":2022,"id":44572,"datarank":0.8435809213710949,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.3548664406678725,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.3548664406678725,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":25,"citers_with_citation_signal":17,"citers_with_endowment":17,"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":209635,"name":"Zhonghui Guan","orcid":"0000-0001-5992-8370","position":1,"is_corresponding":false},{"id":209634,"name":"Jiao Chen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34625907","pmcid":"PMC8786763","openalex_id":"https://openalex.org/W3203173174","authors":[],"funders":[{"funder_name":"national institute of neurological disorders and stroke","grant_id":"R01NS121144","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01NS121144-03","title":"Mechanism of microglia proliferation"}],"total_grants":2,"fwci":1.7404,"citation_percentile":0.87257939,"influential_citations":0,"citation_trend":[{"year":2022,"count":5},{"year":2023,"count":6},{"year":2024,"count":5},{"year":2025,"count":6},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s12035-021-02584-7.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s12035-021-02584-7.pdf","host_type":"HYBRID"},{"url":"https://link.springer.com/content/pdf/10.1007/s12035-021-02584-7.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s12035-021-02584-7/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s12035-021-02584-7","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34625907","host_type":"repository"},{"url":"https://escholarship.org/uc/item/6591q2b6","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8786763","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8786763","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8786763?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1007/s12035-021-02584-7","host_type":""},{"url":"https://dx.doi.org/10.1007/s12035-021-02584-7","host_type":""},{"url":"https://escholarship.org/content/qt6591q2b6/qt6591q2b6.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1007/s12035-021-02584-7","host_type":""}],"fields_of_study":["Neuroblastoma Research and Treatments","Glioma Diagnosis and Treatment","Microtubule and mitosis dynamics","Biology","Medicine","0301 basic medicine","03 medical and health sciences","0303 health sciences","Animals","Cell Proliferation","Lateral Ventricles","Mice","Mice, Transgenic","N-Myc Proto-Oncogene Protein","Neural Stem Cells","Neurogenesis","Olfactory Bulb","Oligodendroglia"],"mesh_terms":["N-Myc Proto-Oncogene Protein","Animals","Mice, Transgenic","Olfactory Bulb","Oligodendroglia","Lateral Ventricles","Cell Proliferation","Mice","Neurogenesis","Neural Stem Cells"],"keywords":["Neuroblast","Subgranular zone","Neurogenesis","Doublecortin","Subventricular zone","Biology","Neural stem cell","Cancer research","Neuroblastoma","Cell biology","Neuroscience","Stem cell","Central nervous system","Cell culture","Genetics","Dentate gyrus","Adult","Mycn","Oligodendrogenesis","570","610","Mice, Transgenic","Transgenic","Article","Mice","Rare Diseases","Neural Stem Cells","Clinical Research","Lateral Ventricles","Psychology","Animals","Cancer","Cell Proliferation","N-Myc Proto-Oncogene Protein","Neurology & Neurosurgery","Neurosciences","Stem Cell Research","Olfactory Bulb","Brain Disorders","Oligodendroglia","Neurological","Stem Cell Research - Nonembryonic - Non-Human","Cognitive Sciences"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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