{"doi":"10.1101/2025.09.22.677893","title":"Establishing a continuum of cell types in the visual cortex","abstract":"The mammalian cerebral cortex is composed of neurons whose properties vary in a continuous fashion rather than falling into discrete cell types. In the mouse visual cortex, excitatory neurons in layer 2 and 3 (L2/3) form such a continuum along cortical depth, patterned by the graded expression of hundreds of genes. Here we sought to understand how this continuum develops and contributes to cortical wiring. Using single-nucleus multiomics (RNA- and ATAC-Seq) and spatial transcriptomics, we show that the L2/3 continuum is established in two phases. During the first postnatal week, a genetically hardwired program establishes a primitive continuum of cell identities spanning the depth of L2/3. The second program, promoted by visual experience, is later superimposed upon the preexisting continuum. This second phase is driven by activity-regulated transcription factors that drive the L2/3 depth-dependent expression of genes linked to synaptic function and plasticity. We show that neurons at different positions along the L2/3 continuum project preferentially to distinct higher visual areas and that visual deprivation disrupts targeting to some higher visual areas while sparing others. Thus, cortical continua emerge through a stepwise process in which genetic programs and sensory experience specify neuronal identity and sculpt intracortical wiring specificity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556777,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9388,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":38370,"name":"Fangming Xie","orcid":"0000-0001-5232-1648","position":1,"is_corresponding":false},{"id":275177,"name":"Salwan Butrus","orcid":"0000-0001-8679-3715","position":2,"is_corresponding":false},{"id":1023832,"name":"Runzhe Xu","orcid":"0000-0002-5364-4112","position":3,"is_corresponding":false},{"id":777168,"name":"Zhiqun Tan","orcid":"0000-0002-2235-4577","position":4,"is_corresponding":false},{"id":1456442,"name":"Ryan Gorzek","orcid":"0000-0002-8320-0416","position":5,"is_corresponding":false},{"id":565616,"name":"Parmis Mirshahidi","orcid":null,"position":6,"is_corresponding":false},{"id":313118,"name":"Elaine Tring","orcid":null,"position":7,"is_corresponding":false},{"id":1456866,"name":"Sanjana Suresh","orcid":null,"position":8,"is_corresponding":false},{"id":716628,"name":"Jinho Kim","orcid":"0000-0002-4675-4612","position":9,"is_corresponding":false},{"id":1456443,"name":"Greg Fleishman","orcid":"0000-0003-1879-6521","position":10,"is_corresponding":false},{"id":311837,"name":"Liming Tan","orcid":"0000-0002-7034-0321","position":11,"is_corresponding":false},{"id":311838,"name":"Dario L. Ringach","orcid":"0000-0001-6439-334X","position":12,"is_corresponding":false},{"id":311839,"name":"Joshua T. Trachtenberg","orcid":"0000-0002-5041-774X","position":13,"is_corresponding":false},{"id":254688,"name":"Xiangmin Xu","orcid":"0000-0002-5828-1533","position":14,"is_corresponding":false},{"id":231545,"name":"S Lawrence Zipursky","orcid":"0000-0001-5630-7181","position":15,"is_corresponding":false},{"id":20632,"name":"Karthik Shekhar","orcid":"0000-0003-4349-6600","position":16,"is_corresponding":false},{"id":1456444,"name":"Saumya Jain","orcid":"0000-0001-7442-7670","position":17,"is_corresponding":false},{"id":1041540,"name":"Juyoun Yoo","orcid":"0000-0002-4600-7094","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:55:13.130091Z","pmid":"41040235","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":[]}