{"id":"https://openalex.org/W7216176387","doi":"https://doi.org/10.64898/2026.09.30.755469","title":"BMP4 Restricts Axonal Ramification and Bouton Density in Cholinergic Projections from the Basal Forebrain","display_name":"BMP4 Restricts Axonal Ramification and Bouton Density in Cholinergic Projections from the Basal Forebrain","publication_year":2026,"publication_date":"2026-10-02","ids":{"openalex":"https://openalex.org/W7216176387","doi":"https://doi.org/10.64898/2026.09.30.755469"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.30.755469","doi":"https://doi.org/10.64898/2026.09.30.755469","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.30.755469","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/02/2026.09.30.755469.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/02/2026.09.30.755469.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5033452050","display_name":"Takahito Higashi","orcid":"https://orcid.org/0009-0009-6044-0423","observed_orcids":["https://orcid.org/0009-0009-6044-0423"]},"institutions":[{"id":"https://openalex.org/I53888640","display_name":"National Defense Medical College","ror":"https://ror.org/02e4qbj88","country_code":"JP","type":"education","lineage":["https://openalex.org/I53888640"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Takahito Higashi","raw_affiliation_strings":["National Defense Medical College;"],"raw_orcid":"https://orcid.org/0009-0009-6044-0423","affiliations":[{"raw_affiliation_string":"National Defense Medical College;","institution_ids":["https://openalex.org/I53888640"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011766068","display_name":"Yasushi Kobayashi","orcid":"https://orcid.org/0000-0001-5072-5040","observed_orcids":["https://orcid.org/0000-0001-5072-5040"]},"institutions":[{"id":"https://openalex.org/I53888640","display_name":"National Defense Medical College","ror":"https://ror.org/02e4qbj88","country_code":"JP","type":"education","lineage":["https://openalex.org/I53888640"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yasushi Kobayashi","raw_affiliation_strings":["National Defense Medical College;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"National Defense Medical College;","institution_ids":["https://openalex.org/I53888640"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Akiko Seki","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210136522","display_name":"Tokyo Women's Medical University","ror":"https://ror.org/03kjjhe36","country_code":"JP","type":"education","lineage":["https://openalex.org/I4210136522"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Akiko Seki","raw_affiliation_strings":["Tokyo Women's Medical University;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Tokyo Women's Medical University;","institution_ids":["https://openalex.org/I4210136522"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054212150","display_name":"Shigeo Okabe","orcid":"https://orcid.org/0000-0003-1216-8890","observed_orcids":["https://orcid.org/0000-0003-1216-8890"]},"institutions":[{"id":"https://openalex.org/I2800939219","display_name":"RIKEN Center for Brain Science","ror":"https://ror.org/04j1n1c04","country_code":"JP","type":"facility","lineage":["https://openalex.org/I2800939219","https://openalex.org/I4210110652"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Shigeo Okabe","raw_affiliation_strings":["RIKEN Center for Brain Science"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"RIKEN Center for Brain Science","institution_ids":["https://openalex.org/I2800939219"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5110217012","display_name":"Kiyomasa Nishii","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I53888640","display_name":"National Defense Medical College","ror":"https://ror.org/02e4qbj88","country_code":"JP","type":"education","lineage":["https://openalex.org/I53888640"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Kiyomasa Nishii","raw_affiliation_strings":["National Defense Medical College;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"National Defense Medical College;","institution_ids":["https://openalex.org/I53888640"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5033452050"],"corresponding_institution_ids":["https://openalex.org/I53888640"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12061","display_name":"Axon Guidance and Neuronal Signaling","score":0.7865999937057495,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12061","display_name":"Axon Guidance and Neuronal Signaling","score":0.7865999937057495,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10077","display_name":"Neuroscience and Neuropharmacology Research","score":0.16580000519752502,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10608","display_name":"Neurogenesis and neuroplasticity mechanisms","score":0.027300000190734863,"subfield":{"id":"https://openalex.org/subfields/2806","display_name":"Developmental Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/bmp4","display_name":"BMP4","score":0.9990000128746033},{"id":"https://openalex.org/keywords/cholinergic-neurons","display_name":"cholinergic neurons","score":0.7720000147819519},{"id":"https://openalex.org/keywords/basal-forebrain","display_name":"basal forebrain","score":0.9739999771118164},{"id":"https://openalex.org/keywords/synaptogenesis","display_name":"synaptogenesis","score":0.7630000114440918},{"id":"https://openalex.org/keywords/neocortex","display_name":"neocortex","score":0.6370000243186951},{"id":"https://openalex.org/keywords/hippocampus","display_name":"hippocampus","score":0.8659999966621399},{"id":"https://openalex.org/keywords/amygdala","display_name":"amygdala","score":0.9990000128746033},{"id":"https://openalex.org/keywords/cholinergic-projections","display_name":"cholinergic projections","score":0.7329999804496765},{"id":"https://openalex.org/keywords/neural-circuit-maturation","display_name":"neural circuit maturation","score":0.8159999847412109}],"concepts":[{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.8342000246047974},{"id":"https://openalex.org/C104966671","wikidata":"https://www.wikidata.org/wiki/Q12167532","display_name":"Cholinergic neuron","level":3,"score":0.7968000173568726},{"id":"https://openalex.org/C22885893","wikidata":"https://www.wikidata.org/wiki/Q4862743","display_name":"Cholinergic","level":2,"score":0.784500002861023},{"id":"https://openalex.org/C2776287375","wikidata":"https://www.wikidata.org/wiki/Q3407681","display_name":"Basal forebrain","level":3,"score":0.762499988079071},{"id":"https://openalex.org/C2777222312","wikidata":"https://www.wikidata.org/wiki/Q726562","display_name":"Neocortex","level":2,"score":0.6324999928474426},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6200000047683716},{"id":"https://openalex.org/C2779530196","wikidata":"https://www.wikidata.org/wiki/Q178999","display_name":"Axon","level":2,"score":0.6123999953269958},{"id":"https://openalex.org/C127445978","wikidata":"https://www.wikidata.org/wiki/Q187181","display_name":"Synapse","level":2,"score":0.5432000160217285},{"id":"https://openalex.org/C2779715522","wikidata":"https://www.wikidata.org/wiki/Q507027","display_name":"Forebrain","level":3,"score":0.4528999924659729},{"id":"https://openalex.org/C164659718","wikidata":"https://www.wikidata.org/wiki/Q5159266","display_name":"Conditional gene knockout","level":4,"score":0.41530001163482666},{"id":"https://openalex.org/C69125201","wikidata":"https://www.wikidata.org/wiki/Q2034716","display_name":"Axon guidance","level":3,"score":0.39809998869895935},{"id":"https://openalex.org/C2780648746","wikidata":"https://www.wikidata.org/wiki/Q28208871","display_name":"Glutamatergic","level":4,"score":0.3659000098705292},{"id":"https://openalex.org/C118403218","wikidata":"https://www.wikidata.org/wiki/Q43283","display_name":"Biological neural network","level":2,"score":0.35749998688697815},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3474000096321106},{"id":"https://openalex.org/C148762608","wikidata":"https://www.wikidata.org/wiki/Q3748185","display_name":"Hippocampal formation","level":2,"score":0.3386000096797943},{"id":"https://openalex.org/C2778794669","wikidata":"https://www.wikidata.org/wiki/Q43054","display_name":"Neuron","level":2,"score":0.31690001487731934},{"id":"https://openalex.org/C4746552","wikidata":"https://www.wikidata.org/wiki/Q1456827","display_name":"Neurogenesis","level":2,"score":0.3154999911785126},{"id":"https://openalex.org/C2775910092","wikidata":"https://www.wikidata.org/wiki/Q180623","display_name":"Acetylcholine","level":2,"score":0.3138999938964844},{"id":"https://openalex.org/C200707615","wikidata":"https://www.wikidata.org/wiki/Q13652744","display_name":"Neuroepithelial cell","level":4,"score":0.30790001153945923},{"id":"https://openalex.org/C2910204272","wikidata":"https://www.wikidata.org/wiki/Q4862743","display_name":"Cholinergic Fibers","level":4,"score":0.2948000133037567},{"id":"https://openalex.org/C29694410","wikidata":"https://www.wikidata.org/wiki/Q7540236","display_name":"Slice preparation","level":3,"score":0.29319998621940613},{"id":"https://openalex.org/C105702510","wikidata":"https://www.wikidata.org/wiki/Q514","display_name":"Anatomy","level":1,"score":0.2825999855995178},{"id":"https://openalex.org/C74254510","wikidata":"https://www.wikidata.org/wiki/Q7240508","display_name":"Premovement neuronal activity","level":2,"score":0.27399998903274536},{"id":"https://openalex.org/C2776219046","wikidata":"https://www.wikidata.org/wiki/Q162657","display_name":"Neurotransmitter","level":3,"score":0.27320000529289246},{"id":"https://openalex.org/C113246987","wikidata":"https://www.wikidata.org/wiki/Q1534415","display_name":"Neurite","level":3,"score":0.2712000012397766},{"id":"https://openalex.org/C25274449","wikidata":"https://www.wikidata.org/wiki/Q1805481","display_name":"Long-term potentiation","level":3,"score":0.26109999418258667},{"id":"https://openalex.org/C135903288","wikidata":"https://www.wikidata.org/wiki/Q559423","display_name":"Growth cone","level":3,"score":0.2603999972343445},{"id":"https://openalex.org/C2777918570","wikidata":"https://www.wikidata.org/wiki/Q2423067","display_name":"Axon terminal","level":3,"score":0.2583000063896179},{"id":"https://openalex.org/C84248122","wikidata":"https://www.wikidata.org/wiki/Q5256671","display_name":"Dendrite (mathematics)","level":2,"score":0.25619998574256897},{"id":"https://openalex.org/C529278444","wikidata":"https://www.wikidata.org/wiki/Q47273","display_name":"Central nervous system","level":2,"score":0.25600001215934753},{"id":"https://openalex.org/C174884520","wikidata":"https://www.wikidata.org/wiki/Q902079","display_name":"Dendritic spine","level":3,"score":0.2540999948978424}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.30.755469","doi":"https://doi.org/10.64898/2026.09.30.755469","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.30.755469","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/02/2026.09.30.755469.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.30.755469","doi":"https://doi.org/10.64898/2026.09.30.755469","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.30.755469","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/02/2026.09.30.755469.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.46810001134872437,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320313900","display_name":"National Defense Medical College","ror":"https://ror.org/02e4qbj88"},{"id":"https://openalex.org/F4320334764","display_name":"Japan Society for the Promotion of Science","ror":"https://ror.org/00hhkn466"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7216176387.pdf","grobid_xml":"https://content.openalex.org/works/W7216176387.grobid-xml"},"referenced_works_count":51,"referenced_works":["https://openalex.org/W1561541164","https://openalex.org/W1974261580","https://openalex.org/W1987332330","https://openalex.org/W1991212898","https://openalex.org/W2018434736","https://openalex.org/W2030777833","https://openalex.org/W2035051064","https://openalex.org/W2040268226","https://openalex.org/W2040868835","https://openalex.org/W2045621697","https://openalex.org/W2047113736","https://openalex.org/W2053225292","https://openalex.org/W2067829194","https://openalex.org/W2078299830","https://openalex.org/W2078757441","https://openalex.org/W2086054038","https://openalex.org/W2100212553","https://openalex.org/W2103669147","https://openalex.org/W2104010513","https://openalex.org/W2112903125","https://openalex.org/W2115444433","https://openalex.org/W2118888847","https://openalex.org/W2130094577","https://openalex.org/W2135585335","https://openalex.org/W2136314718","https://openalex.org/W2141393682","https://openalex.org/W2153065561","https://openalex.org/W2162870648","https://openalex.org/W2213750320","https://openalex.org/W2523262515","https://openalex.org/W2607283788","https://openalex.org/W2609602214","https://openalex.org/W2754385975","https://openalex.org/W2777126142","https://openalex.org/W2784817310","https://openalex.org/W2883601426","https://openalex.org/W2894977457","https://openalex.org/W2937445305","https://openalex.org/W2959600977","https://openalex.org/W2964140141","https://openalex.org/W3038435474","https://openalex.org/W3108465191","https://openalex.org/W3127865527","https://openalex.org/W3158326523","https://openalex.org/W3165484394","https://openalex.org/W3213964818","https://openalex.org/W4211160592","https://openalex.org/W4221002516","https://openalex.org/W4308147376","https://openalex.org/W4394904477","https://openalex.org/W4401606984"],"related_works":["https://openalex.org/W6977877440","https://openalex.org/W2784817310","https://openalex.org/W2409672700","https://openalex.org/W2086054038","https://openalex.org/W2048900838","https://openalex.org/W2002171173","https://openalex.org/W2167556574","https://openalex.org/W4220827900","https://openalex.org/W2020305002","https://openalex.org/W2048314677"],"abstract_inverted_index":{"Axonal":[0],"projections":[1],"and":[2,15,22,36,147,156,170,207],"precise":[3],"synapse":[4,37,98],"formation":[5,206],"are":[6,148],"essential":[7,149],"for":[8,150],"the":[9,39,101,114,145,167,179,190],"establishment":[10],"of":[11,116,203],"functional":[12],"neural":[13,69,222],"circuits,":[14],"their":[16,49],"dysregulation":[17],"contributes":[18],"to":[19,96,216],"various":[20],"psychiatric":[21],"neurodegenerative":[23],"disorders.":[24],"Although":[25],"numerous":[26],"extracellular":[27],"cues":[28],"secreted":[29],"from":[30],"surrounding":[31],"tissues":[32],"regulate":[33,45],"axon":[34,164],"guidance":[35],"formation,":[38,99],"mechanisms":[40],"by":[41],"which":[42],"neurons":[43,87,141],"locally":[44,93,215],"terminal":[46,106,205],"patterning":[47,71],"within":[48],"projection":[50],"fields":[51],"remain":[52],"poorly":[53],"understood.":[54],"Bone":[55],"morphogenetic":[56],"protein":[57],"4":[58],"(BMP4)":[59],"is":[60,65],"a":[61,200],"classical":[62],"morphogen":[63],"that":[64,89,103,196,211],"involved":[66],"in":[67,81,118,136,166,178,189],"early":[68],"tube":[70],"during":[72,221],"development.":[73],"However,":[74],"its":[75],"postnatal":[76,119],"function":[77],"remains":[78],"unclear.":[79],"Previous":[80],"vitro":[82],"studies":[83],"using":[84,123],"hippocampal":[85],"glutamatergic":[86],"demonstrated":[88],"BMP4":[90,104,117,197,212],"can":[91],"act":[92,214],"on":[94],"axons":[95],"suppress":[97],"raising":[100],"possibility":[102],"regulates":[105],"differentiation":[107],"after":[108],"target":[109],"innervation.":[110],"Here,":[111],"we":[112],"investigated":[113],"role":[115],"cholinergic":[120,124,140,163,186,204,218],"circuit":[121,223],"development":[122],"neuron-specific":[125],"Bmp4":[126,158],"conditional":[127],"knockout":[128],"(Bmp4":[129],"cKO)":[130],"mice,":[131],"with":[132],"adult":[133],"analyses":[134],"performed":[135],"males.":[137],"Basal":[138],"forebrain":[139],"project":[142],"extensively":[143],"throughout":[144],"neocortex":[146,180],"higher":[151],"brain":[152],"functions,":[153],"including":[154],"arousal":[155],"attention.":[157],"cKO":[159],"mice":[160],"exhibited":[161],"increased":[162,175],"terminals":[165],"neocortex,":[168],"hippocampus,":[169],"amygdala,":[171],"as":[172,174,199],"well":[173],"axonal":[176,208,219],"ramification":[177],"without":[181],"affecting":[182],"cytoarchitectonic":[183],"organization":[184],"or":[185],"neuron":[187],"numbers":[188],"basal":[191],"forebrain.":[192],"These":[193],"findings":[194],"demonstrate":[195],"functions":[198],"negative":[201],"regulator":[202],"arborization,":[209],"suggesting":[210],"may":[213],"restrict":[217],"expansion":[220],"maturation.":[224]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-10-03T00:00:00"}