{"doi":"10.1101/2023.12.12.571306","title":"Differential developmental blueprints of organ-intrinsic nervous systems","abstract":"Abstract The organ-intrinsic nervous system is a major interface between visceral organs and the brain, mediating important sensory and regulatory functions in the body-brain axis and serving as critical local processors for organ homeostasis. Molecularly, anatomically, and functionally, organ-intrinsic neurons are highly specialized for their host organs. However, the underlying mechanism that drives this specialization is largely unknown. Here, we describe the differential strategies utilized to achieve organ-specific organization between the enteric nervous system (ENS) 1 and the intrinsic cardiac nervous system (ICNS) 2 , a neuronal network essential for heart performance but poorly characterized. Integrating high-resolution whole-embryo imaging, single-cell genomics, spatial transcriptomics, proteomics, and bioinformatics, we uncover that unlike the ENS which is highly mobile and colonizes the entire gastrointestinal (GI) tract, the ICNS uses a rich set of extracellular matrix (ECM) genes that match with surrounding heart cells and an intermediate dedicated neuronal progenitor state to stabilize itself for a ‘beads-on-the-necklace’ organization on heart atria. While ICNS- and ENS-precursors are genetically similar, their differentiation paths are influenced by their host-organs, leading to distinct mature neuron types. Co-culturing ENS-precursors with heart cells shifts their identity towards the ICNS and induces the expression of heart-matching ECM genes. Our cross-organ study thus reveals fundamental principles for the maturation and specialization of organ-intrinsic neurons.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395493,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":254209,"name":"Yingxin Lin","orcid":"0000-0002-4299-7326","position":1,"is_corresponding":false},{"id":1170773,"name":"Yunshan Guo","orcid":"0000-0001-6671-3300","position":2,"is_corresponding":false},{"id":841946,"name":"Qian Xu","orcid":"0000-0003-4542-0749","position":3,"is_corresponding":false},{"id":1171117,"name":"Yuancheng Shao","orcid":null,"position":4,"is_corresponding":false},{"id":800895,"name":"Ruiqi Wang","orcid":"0000-0002-9403-7693","position":5,"is_corresponding":false},{"id":1170774,"name":"Dominic Yin","orcid":"0000-0001-7733-9326","position":6,"is_corresponding":false},{"id":971342,"name":"Jia Zhao","orcid":"0000-0002-7801-5064","position":7,"is_corresponding":false},{"id":865091,"name":"Lawrence H. Young","orcid":"0000-0003-0295-7298","position":8,"is_corresponding":false},{"id":2737,"name":"Luca Pinello","orcid":"0000-0003-1195-9607","position":9,"is_corresponding":false},{"id":69461,"name":"Le Zhang","orcid":"0000-0002-4860-831X","position":10,"is_corresponding":false},{"id":841948,"name":"Rui B. Chang","orcid":"0000-0001-6953-2943","position":11,"is_corresponding":false},{"id":1170772,"name":"I‐Uen Hsu","orcid":"0000-0002-4089-6601","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T01:19:22.857556Z","pmid":"38168446","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":[]}