{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T20:23:08Z","timestamp":1794687788810,"version":"4.9.1"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"8122","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2026,7,9]]},"DOI":"10.1038\/s41586-026-10490-y","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:02:41Z","timestamp":1778684561000},"page":"429-437","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lineage and organ signals sequentially build organ intrinsic nervous systems"],"prefix":"10.1038","volume":"655","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4089-6601","authenticated-orcid":false,"given":"I-Uen Yvonne","family":"Hsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9107-8852","authenticated-orcid":false,"given":"Jia","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4299-7326","authenticated-orcid":false,"given":"Yingxin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunshan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian J.","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuancheng","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7176-9560","authenticated-orcid":false,"given":"Ruiqi L.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7733-9326","authenticated-orcid":false,"given":"Dominic","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kakali","family":"Ghoshal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rida","family":"Mourad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambra","family":"Pozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4889-8131","authenticated-orcid":false,"given":"Carmen M.","family":"Halabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence H.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-9607","authenticated-orcid":false,"given":"Hongyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4860-831X","authenticated-orcid":false,"given":"Le","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6953-2943","authenticated-orcid":false,"given":"Rui B.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"10490_CR1","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1152\/physrev.00018.2022","volume":"103","author":"KA Sharkey","year":"2023","unstructured":"Sharkey, K. A. & Mawe, G. M. The enteric nervous system. Physiol. Rev. 103, 1487\u20131564 (2023).","journal-title":"Physiol. Rev."},{"key":"10490_CR2","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/nrgastro.2016.107","volume":"13","author":"M Rao","year":"2016","unstructured":"Rao, M. & Gershon, M. D. The bowel and beyond: the enteric nervous system in neurological disorders. Nat. Rev. Gastroenterol. Hepatol. 13, 517\u2013528 (2016).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10490_CR3","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1113\/expphysiol.2007.041178","volume":"93","author":"JA Armour","year":"2008","unstructured":"Armour, J. A. Potential clinical relevance of the \u2018little brain\u2019 on the mammalian heart. Exp. Physiol. 93, 165\u2013176 (2008).","journal-title":"Exp. Physiol."},{"key":"10490_CR4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.autneu.2016.08.006","volume":"199","author":"E Wake","year":"2016","unstructured":"Wake, E. & Brack, K. Characterization of the intrinsic cardiac nervous system. Auton. Neurosci. 199, 3\u201316 (2016).","journal-title":"Auton. Neurosci."},{"key":"10490_CR5","doi-asserted-by":"publisher","DOI":"10.1242\/dev.202254","volume":"151","author":"RH Agerskov","year":"2024","unstructured":"Agerskov, R. H. & Nyeng, P. Innervation of the pancreas in development and disease. Development. 151, e202254 (2024).","journal-title":"Development"},{"key":"10490_CR6","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3389\/fnins.2019.00021","volume":"13","author":"W Li","year":"2019","unstructured":"Li, W., Yu, G., Liu, Y. & Sha, L. Intrapancreatic ganglia and neural regulation of pancreatic endocrine secretion. Front. Neurosci. 13, 21 (2019).","journal-title":"Front. Neurosci."},{"key":"10490_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-08655-6","volume":"12","author":"AB Pincus","year":"2022","unstructured":"Pincus, A. B. et al. Multicolor labeling of airway neurons and analysis of parasympathetic heterogeneity. Sci. Rep. 12, 5006 (2022).","journal-title":"Sci. Rep."},{"key":"10490_CR8","volume":"7","author":"L Fedele","year":"2020","unstructured":"Fedele, L. & Brand, T. The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction. J. Cardiovasc. Dev. Dis. 7, 54 (2020).","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"10490_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09770-1","volume":"10","author":"PS Rajendran","year":"2019","unstructured":"Rajendran, P. S. et al. Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies. Nat. Commun. 10, 1944 (2019).","journal-title":"Nat. Commun."},{"key":"10490_CR10","doi-asserted-by":"publisher","unstructured":"Xu, Q. J. et al. Two specialized intrinsic cardiac neuron types safeguard heart homeostasis and stress resilience. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.06.13.659555 (2025).","DOI":"10.1101\/2025.06.13.659555"},{"key":"10490_CR11","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/s41586-022-04760-8","volume":"606","author":"A Veerakumar","year":"2022","unstructured":"Veerakumar, A., Yung, A. R., Liu, Y. & Krasnow, M. A. Molecularly defined circuits for cardiovascular and cardiopulmonary control. Nature 606, 739\u2013746 (2022).","journal-title":"Nature"},{"key":"10490_CR12","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41586-024-07608-5","volume":"631","author":"Y Su","year":"2024","unstructured":"Su, Y. et al. Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity. Nature 631, 601\u2013609 (2024).","journal-title":"Nature"},{"key":"10490_CR13","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1002\/cne.901010212","volume":"101","author":"CL Yntema","year":"1954","unstructured":"Yntema, C. L. & Hammond, W. S. The origin of intrinsic ganglia of trunk viscera from vagal neural crest in the chick embryo. J. Comp. Neurol. 101, 515\u2013541 (1954).","journal-title":"J. Comp. Neurol."},{"key":"10490_CR14","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/0016-6480(77)90055-7","volume":"33","author":"J Fontaine","year":"1977","unstructured":"Fontaine, J., Le Lievre, C. & Le Douarin, N. M. What is the developmental fate of the neural crest cells which migrate into the pancreas in the avian embryo? Gen. Comp. Endocrinol. 33, 394\u2013404 (1977).","journal-title":"Gen. Comp. Endocrinol."},{"key":"10490_CR15","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1111\/j.1469-7580.2010.01295.x","volume":"217","author":"LJ Freem","year":"2010","unstructured":"Freem, L. J. et al. The intrinsic innervation of the lung is derived from neural crest cells as shown by optical projection tomography in Wnt1-Cre;YFP reporter mice. J. Anat. 217, 651\u2013664 (2010).","journal-title":"J. Anat."},{"key":"10490_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1469-7580.2007.00833.x","volume":"212","author":"V Hildreth","year":"2008","unstructured":"Hildreth, V. et al. Cells migrating from the neural crest contribute to the innervation of the venous pole of the heart. J. Anat. 212, 1\u201311 (2008).","journal-title":"J. Anat."},{"key":"10490_CR17","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1016\/j.cell.2020.08.003","volume":"182","author":"E Drokhlyansky","year":"2020","unstructured":"Drokhlyansky, E. et al. The human and mouse enteric nervous system at single-cell resolution. Cell 182, 1606\u20131622.e1623 (2020).","journal-title":"Cell"},{"key":"10490_CR18","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/s41593-020-00736-x","volume":"24","author":"K Morarach","year":"2021","unstructured":"Morarach, K. et al. Diversification of molecularly defined myenteric neuron classes revealed by single-cell RNA sequencing. Nat. Neurosci. 24, 34\u201346 (2021).","journal-title":"Nat. Neurosci."},{"key":"10490_CR19","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/s41593-025-01962-x","volume":"28","author":"W Li","year":"2025","unstructured":"Li, W. et al. The transcriptomes, connections and development of submucosal neuron classes in the mouse small intestine. Nat. Neurosci. 28, 1146\u20131159 (2025).","journal-title":"Nat. Neurosci."},{"key":"10490_CR20","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1016\/j.hrthm.2022.04.012","volume":"19","author":"G Lizot","year":"2022","unstructured":"Lizot, G. et al. Molecular and functional characterization of the mouse intrinsic cardiac nervous system. Heart Rhythm 19, 1352\u20131362 (2022).","journal-title":"Heart Rhythm"},{"key":"10490_CR21","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1161\/CIRCRESAHA.120.318458","volume":"128","author":"P Hanna","year":"2021","unstructured":"Hanna, P. et al. Innervation and neuronal control of the mammalian sinoatrial node a comprehensive atlas. Circ. Res. 128, 1279\u20131296 (2021).","journal-title":"Circ. Res."},{"key":"10490_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101140","volume":"23","author":"S Achanta","year":"2020","unstructured":"Achanta, S. et al. A comprehensive integrated anatomical and molecular atlas of rat intrinsic cardiac nervous system. iScience 23, 101140 (2020).","journal-title":"iScience"},{"key":"10490_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102713","volume":"24","author":"A Moss","year":"2021","unstructured":"Moss, A. et al. A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system. iScience 24, 102713 (2021).","journal-title":"iScience"},{"key":"10490_CR24","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1126\/science.3952494","volume":"231","author":"NM Le Douarin","year":"1986","unstructured":"Le Douarin, N. M. Cell line segregation during peripheral nervous system ontogeny. Science 231, 1515\u20131522 (1986).","journal-title":"Science"},{"key":"10490_CR25","doi-asserted-by":"publisher","first-page":"4637","DOI":"10.1242\/dev.01350","volume":"131","author":"NM Le Douarin","year":"2004","unstructured":"Le Douarin, N. M., Creuzet, S., Couly, G. & Dupin, E. Neural crest cell plasticity and its limits. Development 131, 4637\u20134650 (2004).","journal-title":"Development"},{"key":"10490_CR26","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/0012-1606(77)90269-X","volume":"56","author":"PH Patterson","year":"1977","unstructured":"Patterson, P. H. & Chun, L. L. The induction of acetylcholine synthesis in primary cultures of dissociated rat sympathetic neurons I. Effects of conditioned medium. Dev. Biol. 56, 263\u2013280 (1977).","journal-title":"Dev. Biol."},{"key":"10490_CR27","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/0012-1606(77)90144-0","volume":"60","author":"PH Patterson","year":"1977","unstructured":"Patterson, P. H. & Chun, L. L. Y. The induction of acetylcholine synthesis in primary cultures of dissociated rat sympathetic neurons: II. Developmental aspects. Dev. Biol. 60, 473\u2013481 (1977).","journal-title":"Dev. Biol."},{"key":"10490_CR28","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1126\/science.aaf2729","volume":"352","author":"M Simoes-Costa","year":"2016","unstructured":"Simoes-Costa, M. & Bronner, M. E. Reprogramming of avian neural crest axial identity and cell fate. Science 352, 1570\u20131573 (2016).","journal-title":"Science"},{"key":"10490_CR29","doi-asserted-by":"publisher","DOI":"10.1126\/science.aas9536","volume":"364","author":"R Soldatov","year":"2019","unstructured":"Soldatov, R. et al. Spatiotemporal structure of cell fate decisions in murine neural crest. Science 364, eaas9536 (2019).","journal-title":"Science"},{"key":"10490_CR30","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1242\/dev.015859","volume":"135","author":"N Nekrep","year":"2008","unstructured":"Nekrep, N., Wang, J., Miyatsuka, T. & German, M. S. Signals from the neural crest regulate beta-cell mass in the pancreas. Development 135, 2151\u20132160 (2008).","journal-title":"Development"},{"key":"10490_CR31","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1152\/ajpgi.00452.2012","volume":"305","author":"JI Lake","year":"2013","unstructured":"Lake, J. I. & Heuckeroth, R. O. Enteric nervous system development: migration, differentiation, and disease. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G1\u201324 (2013).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10490_CR32","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1002\/aja.1001940207","volume":"194","author":"AL Kirchgessner","year":"1992","unstructured":"Kirchgessner, A. L., Adlersberg, M. A. & Gershon, M. D. Colonization of the developing pancreas by neural precursors from the bowel. Dev. Dyn. 194, 142\u2013154 (1992).","journal-title":"Dev. Dyn."},{"key":"10490_CR33","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1002\/dvdy.1124","volume":"221","author":"J Tollet","year":"2001","unstructured":"Tollet, J., Everett, A. W. & Sparrow, M. P. Spatial and temporal distribution of nerves, ganglia, and smooth muscle during the early pseudoglandular stage of fetal mouse lung development. Dev. Dyn. 221, 48\u201360 (2001).","journal-title":"Dev. Dyn."},{"key":"10490_CR34","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1126\/science.1253281","volume":"345","author":"V Dyachuk","year":"2014","unstructured":"Dyachuk, V. et al. Neurodevelopment. Parasympathetic neurons originate from nerve-associated peripheral glial progenitors. Science 345, 82\u201387 (2014).","journal-title":"Science"},{"key":"10490_CR35","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1126\/science.1253286","volume":"345","author":"I Espinosa-Medina","year":"2014","unstructured":"Espinosa-Medina, I. et al. Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors. Science 345, 87\u201390 (2014).","journal-title":"Science"},{"key":"10490_CR36","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.ydbio.2012.01.012","volume":"366","author":"V Sasselli","year":"2012","unstructured":"Sasselli, V., Pachnis, V. & Burns, A. J. The enteric nervous system. Dev. Biol. 366, 64\u201373 (2012).","journal-title":"Dev. Biol."},{"key":"10490_CR37","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.ydbio.2020.12.006","volume":"471","author":"KK Deal","year":"2021","unstructured":"Deal, K. K. et al. Sox10-cre BAC transgenes reveal temporal restriction of mesenchymal cranial neural crest and identify glandular Sox10 expression. Dev. Biol. 471, 119\u2013137 (2021).","journal-title":"Dev. Biol."},{"key":"10490_CR38","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1006\/dbio.1996.0116","volume":"175","author":"H Gardner","year":"1996","unstructured":"Gardner, H., Kreidberg, J., Koteliansky, V. & Jaenisch, R. Deletion of integrin alpha 1 by homologous recombination permits normal murine development but gives rise to a specific deficit in cell adhesion. Dev. Biol. 175, 301\u2013313 (1996).","journal-title":"Dev. Biol."},{"key":"10490_CR39","doi-asserted-by":"publisher","first-page":"4880","DOI":"10.1523\/JNEUROSCI.13-11-04880.1993","volume":"13","author":"KJ Tomaselli","year":"1993","unstructured":"Tomaselli, K. J. et al. Expression of beta 1 integrins in sensory neurons of the dorsal root ganglion and their functions in neurite outgrowth on two laminin isoforms. J. Neurosci. 13, 4880\u20134888 (1993).","journal-title":"J. Neurosci."},{"key":"10490_CR40","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1242\/jcs.106.4.1357","volume":"106","author":"R Perris","year":"1993","unstructured":"Perris, R., Syfrig, J., Paulsson, M. & Bronner-Fraser, M. Molecular mechanisms of neural crest cell attachment and migration on types I and IV collagen. J. Cell Sci. 106, 1357\u20131368 (1993).","journal-title":"J. Cell Sci."},{"key":"10490_CR41","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1002\/jcb.10413","volume":"88","author":"HM Kagan","year":"2003","unstructured":"Kagan, H. M. & Li, W. Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J. Cell. Biochem. 88, 660\u2013672 (2003).","journal-title":"J. Cell. Biochem."},{"key":"10490_CR42","doi-asserted-by":"publisher","first-page":"14387","DOI":"10.1074\/jbc.M210144200","volume":"278","author":"IK Hornstra","year":"2003","unstructured":"Hornstra, I. K. et al. Lysyl oxidase is required for vascular and diaphragmatic development in mice. J. Biol. Chem. 278, 14387\u201314393 (2003).","journal-title":"J. Biol. Chem."},{"key":"10490_CR43","doi-asserted-by":"publisher","first-page":"9879","DOI":"10.1523\/JNEUROSCI.1239-15.2015","volume":"35","author":"T Uesaka","year":"2015","unstructured":"Uesaka, T., Nagashimada, M. & Enomoto, H. Neuronal differentiation in schwann cell lineage underlies postnatal neurogenesis in the enteric nervous system. J. Neurosci. 35, 9879\u20139888 (2015).","journal-title":"J. Neurosci."},{"key":"10490_CR44","doi-asserted-by":"publisher","first-page":"11980","DOI":"10.1073\/pnas.1710308114","volume":"114","author":"I Espinosa-Medina","year":"2017","unstructured":"Espinosa-Medina, I. et al. Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest. Proc. Natl Acad. Sci. USA 114, 11980\u201311985 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10490_CR45","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1387\/ijdb.113438lf","volume":"56","author":"LJ Freem","year":"2012","unstructured":"Freem, L. J., Delalande, J. M., Campbell, A. M., Thapar, N. & Burns, A. J. Lack of organ specific commitment of vagal neural crest cell derivatives as shown by back-transplantation of GFP chicken tissues. Int. J. Dev. Biol. 56, 245\u2013254 (2012).","journal-title":"Int. J. Dev. Biol."},{"key":"10490_CR46","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70281","volume":"6","author":"T Zhao","year":"2025","unstructured":"Zhao, T. et al. Extracellular matrix signaling cues: biological functions, diseases, and therapeutic targets. MedComm 6, e70281 (2025).","journal-title":"MedComm"},{"key":"10490_CR47","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2021.691777","volume":"15","author":"B Lkhagvasuren","year":"2021","unstructured":"Lkhagvasuren, B. et al. Pancreas\u2013brain crosstalk. Front Neuroanat 15, 691777 (2021).","journal-title":"Front Neuroanat"},{"key":"10490_CR48","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.semcdb.2023.01.001","volume":"156","author":"PS Rajendran","year":"2024","unstructured":"Rajendran, P. S. et al. The vagus nerve in cardiovascular physiology and pathophysiology: from evolutionary insights to clinical medicine. Semin. Cell Dev. Biol. 156, 190\u2013200 (2024).","journal-title":"Semin. Cell Dev. Biol."},{"key":"10490_CR49","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143775","volume":"131","author":"A Singh","year":"2021","unstructured":"Singh, A., Dawson, T. M. & Kulkarni, S. Neurodegenerative disorders and gut\u2013brain interactions. J. Clin. Invest. 131, e143775 (2021).","journal-title":"J. Clin. Invest."},{"key":"10490_CR50","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1097\/MOG.0000000000001065","volume":"41","author":"X Hou","year":"2025","unstructured":"Hou, X. & Artis, D. Neuro-immune cell interactions in the regulation of intestinal immune homeostasis. Curr. Opin. Gastroenterol. 41, 38\u201345 (2025).","journal-title":"Curr. Opin. Gastroenterol."},{"key":"10490_CR51","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.cell.2015.03.022","volume":"161","author":"RB Chang","year":"2015","unstructured":"Chang, R. B., Strochlic, D. E., Williams, E. K., Umans, B. D. & Liberles, S. D. Vagal sensory neuron subtypes that differentially control breathing. Cell 161, 622\u2013633 (2015).","journal-title":"Cell"},{"key":"10490_CR52","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1038\/nprot.2015.085","volume":"10","author":"EA Susaki","year":"2015","unstructured":"Susaki, E. A. et al. Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging. Nat. Protoc. 10, 1709\u20131727 (2015).","journal-title":"Nat. Protoc."},{"key":"10490_CR53","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573\u20133587.e3529 (2021).","journal-title":"Cell"},{"key":"10490_CR54","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyad031","volume":"224","author":"The Gene Ontology Consortium","year":"2023","unstructured":"The Gene Ontology Consortium The Gene Ontology knowledgebase in 2023. Genetics 224, iyad031 (2023).","journal-title":"Genetics"},{"key":"10490_CR55","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"The Gene Ontology Consortium","year":"2000","unstructured":"The Gene Ontology Consortium Gene Ontology: tool for the unification of biology. Nat. Genet. 25, 25\u201329 (2000).","journal-title":"Nat. Genet."},{"key":"10490_CR56","doi-asserted-by":"publisher","first-page":"D33","DOI":"10.1093\/nar\/gky822","volume":"47","author":"H Hu","year":"2019","unstructured":"Hu, H. et al. AnimalTFDB 3.0: a comprehensive resource for annotation and prediction of animal transcription factors. Nucleic Acids Res. 47, D33\u2013D38 (2019).","journal-title":"Nucleic Acids Res."},{"key":"10490_CR57","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1126\/science.aad0501","volume":"352","author":"I Tirosh","year":"2016","unstructured":"Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189\u2013196 (2016).","journal-title":"Science"},{"key":"10490_CR58","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/s43588-022-00251-y","volume":"2","author":"J Zhao","year":"2022","unstructured":"Zhao, J. et al. Adversarial domain translation networks for integrating large-scale atlas-level single-cell datasets. Nat. Comput. Sci. 2, 317\u2013330 (2022).","journal-title":"Nat. Comput. Sci."},{"key":"10490_CR59","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41586-018-0414-6","volume":"560","author":"G La Manno","year":"2018","unstructured":"La Manno, G. et al. RNA velocity of single cells. Nature 560, 494\u2013498 (2018).","journal-title":"Nature"},{"key":"10490_CR60","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/s41592-023-01994-w","volume":"21","author":"A Gayoso","year":"2024","unstructured":"Gayoso, A. et al. Deep generative modeling of transcriptional dynamics for RNA velocity analysis in single cells. Nat. Methods 21, 50\u201359 (2024).","journal-title":"Nat. Methods"},{"key":"10490_CR61","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","volume":"566","author":"J Cao","year":"2019","unstructured":"Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496\u2013502 (2019).","journal-title":"Nature"},{"key":"10490_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4772-0","volume":"19","author":"K Street","year":"2018","unstructured":"Street, K. et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19, 477 (2018).","journal-title":"BMC Genomics"},{"key":"10490_CR63","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199512","volume":"148","author":"N Negretti","year":"2021","unstructured":"Negretti, N. et al. A single-cell atlas of mouse lung development. Development 148, dev199512 (2021).","journal-title":"Development"},{"key":"10490_CR64","doi-asserted-by":"publisher","first-page":"3922","DOI":"10.1038\/s41467-018-06176-3","volume":"9","author":"LE Byrnes","year":"2018","unstructured":"Byrnes, L. E. et al. Lineage dynamics of murine pancreatic development at single-cell resolution. Nat. Commun. 9, 3922 (2018).","journal-title":"Nat. Commun."},{"key":"10490_CR65","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35691-7","volume":"13","author":"W Feng","year":"2022","unstructured":"Feng, W. et al. Single-cell transcriptomic analysis identifies murine heart molecular features at embryonic and neonatal stages. Nat. Commun. 13, 7960 (2022).","journal-title":"Nat. Commun."},{"key":"10490_CR66","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/s41586-023-06311-1","volume":"619","author":"K Kanemaru","year":"2023","unstructured":"Kanemaru, K. et al. Spatially resolved multiomics of human cardiac niches. Nature 619, 801\u2013810 (2023).","journal-title":"Nature"},{"key":"10490_CR67","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9","volume":"12","author":"S Jin","year":"2021","unstructured":"Jin, S. et al. Inference and analysis of cell-cell communication using CellChat. Nat. Commun. 12, 1088 (2021).","journal-title":"Nat. Commun."},{"key":"10490_CR68","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/s41586-024-08453-2","volume":"638","author":"D Klein","year":"2025","unstructured":"Klein, D. et al. Mapping cells through time and space with moscot. Nature 638, 1065\u20131075 (2025).","journal-title":"Nature"},{"key":"10490_CR69","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888\u20131902.e1821 (2019).","journal-title":"Cell"},{"key":"10490_CR70","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0","volume":"19","author":"FA Wolf","year":"2018","unstructured":"Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).","journal-title":"Genome Biol."},{"key":"10490_CR71","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1038\/s41586-022-04515-5","volume":"603","author":"Q Zhao","year":"2022","unstructured":"Zhao, Q. et al. A multidimensional coding architecture of the vagal interoceptive system. Nature 603, 878\u2013884 (2022).","journal-title":"Nature"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10490-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10490-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10490-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:02:07Z","timestamp":1783512127000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10490-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":71,"journal-issue":{"issue":"8122","published-print":{"date-parts":[[2026,7,9]]}},"alternative-id":["10490"],"URL":"https:\/\/doi.org\/10.1038\/s41586-026-10490-y","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]},"assertion":[{"value":"12 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}