{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:25:00Z","timestamp":1779909900911,"version":"3.53.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"DOI":"10.1038\/s41390-026-04789-9","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T13:19:38Z","timestamp":1772025578000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["DNER as a novel protein contributes to HSCR pathogenesis: multi-omics combined Mendelian randomization analysis"],"prefix":"10.1038","author":[{"given":"Wei","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baijun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghao","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"4789_CR1","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/s41572-023-00465-y","volume":"9","author":"L Montalva","year":"2023","unstructured":"Montalva, L. et al. Hirschsprung Disease. Nat. Rev. Dis. Prim. 9, 54 (2023).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"4789_CR2","doi-asserted-by":"crossref","unstructured":"Klein, M. & Varga, I. Hirschsprung\u2019s disease-recent understanding of embryonic aspects, etiopathogenesis and future treatment avenues. Medicina (Kaunas) 56, 611 (2020).","DOI":"10.3390\/medicina56110611"},{"key":"4789_CR3","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.jpeds.2005.01.044","volume":"146","author":"F De Lorijn","year":"2005","unstructured":"De Lorijn, F. et al. Diagnosis of Hirschsprung\u2019s disease: a prospective, comparative accuracy study of common tests. J. Pediatr. 146, 787\u2013792 (2005).","journal-title":"J. Pediatr."},{"key":"4789_CR4","doi-asserted-by":"publisher","first-page":"e622","DOI":"10.1016\/j.amjmed.2020.02.022","volume":"133","author":"KA Shair","year":"2020","unstructured":"Shair, K. A. & Edwards, E. Hirschsprung\u2019s disease in an adult. Am. J. Med. 133, e622\u2013e624 (2020).","journal-title":"Am. J. Med."},{"key":"4789_CR5","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/nrgastro.2017.149","volume":"15","author":"RO Heuckeroth","year":"2018","unstructured":"Heuckeroth, R. O. Hirschsprung disease - integrating basic science and clinical medicine to improve outcomes. Nat. Rev. Gastroenterol. Hepatol. 15, 152\u2013167 (2018).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"4789_CR6","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1016\/j.jpedsurg.2012.04.022","volume":"47","author":"KJ Stensrud","year":"2012","unstructured":"Stensrud, K. J., Emblem, R. & Bj\u00f8rnland, K. Late diagnosis of Hirschsprung disease-patient characteristics and results. J. Pediatr. Surg. 47, 1874\u20131879 (2012).","journal-title":"J. Pediatr. Surg."},{"key":"4789_CR7","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj1541","volume":"374","author":"M Pietzner","year":"2021","unstructured":"Pietzner, M. et al. Mapping the proteo-genomic convergence of human diseases. Science 374, eabj1541 (2021).","journal-title":"Science"},{"key":"4789_CR8","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1038\/s41588-021-00978-w","volume":"53","author":"E Ferkingstad","year":"2021","unstructured":"Ferkingstad, E. et al. Large-scale integration of the plasma proteome with genetics and disease. Nat. Genet 53, 1712\u20131721 (2021).","journal-title":"Nat. Genet"},{"key":"4789_CR9","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41586-018-0175-2","volume":"558","author":"BB Sun","year":"2018","unstructured":"Sun, B. B. et al. Genomic atlas of the human plasma proteome. Nature 558, 73\u201379 (2018).","journal-title":"Nature"},{"key":"4789_CR10","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","volume":"622","author":"BB Sun","year":"2023","unstructured":"Sun, B. B. et al. Plasma proteomic associations with genetics and health in the Uk Biobank. Nature 622, 329\u2013338 (2023).","journal-title":"Nature"},{"key":"4789_CR11","doi-asserted-by":"publisher","first-page":"k601","DOI":"10.1136\/bmj.k601","volume":"362","author":"NM Davies","year":"2018","unstructured":"Davies, N. M., Holmes, M. V. & Davey Smith, G. Reading mendelian randomisation studies: a guide, glossary, and checklist for clinicians. Bmj 362, k601 (2018).","journal-title":"Bmj"},{"key":"4789_CR12","doi-asserted-by":"publisher","first-page":"e1004383","DOI":"10.1371\/journal.pgen.1004383","volume":"10","author":"C Giambartolomei","year":"2014","unstructured":"Giambartolomei, C. et al. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet 10, e1004383 (2014).","journal-title":"PLoS Genet"},{"key":"4789_CR13","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/s41586-024-07517-7","volume":"631","author":"DB Mahat","year":"2024","unstructured":"Mahat, D. B. et al. Single-cell nascent Rna sequencing unveils coordinated global transcription. Nature 631, 216\u2013223 (2024).","journal-title":"Nature"},{"key":"4789_CR14","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/nmeth.1315","volume":"6","author":"F Tang","year":"2009","unstructured":"Tang, F. et al. Mrna-Seq whole-transcriptome analysis of a single cell. Nat. Methods 6, 377\u2013382 (2009).","journal-title":"Nat. Methods"},{"key":"4789_CR15","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1001\/jama.2017.17219","volume":"318","author":"CA Emdin","year":"2017","unstructured":"Emdin, C. A., Khera, A. V. & Kathiresan, S. Mendelian randomization. Jama 318, 1925\u20131926 (2017).","journal-title":"Jama"},{"key":"4789_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02317-2","volume":"9","author":"Z Zhu","year":"2018","unstructured":"Zhu, Z. et al. Causal associations between risk factors and common diseases inferred from gwas summary data. Nat. Commun. 9, 224 (2018).","journal-title":"Nat. Commun."},{"key":"4789_CR17","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/s43856-024-00473-3","volume":"4","author":"A Xue","year":"2024","unstructured":"Xue, A. et al. Unravelling the complex causal effects of substance use behaviours on common diseases. Commun. Med (Lond.) 4, 43 (2024).","journal-title":"Commun. Med (Lond.)"},{"key":"4789_CR18","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/340245a0","volume":"340","author":"S Fields","year":"1989","unstructured":"Fields, S. & Song, O. A novel genetic system to detect protein-protein interactions. Nature 340, 245\u2013246 (1989).","journal-title":"Nature"},{"key":"4789_CR19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner, M. et al. Gene ontology: tool for the unification of biology. the gene ontology consortium. Nat. Genet 25, 25\u201329 (2000).","journal-title":"Nat. Genet"},{"key":"4789_CR20","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1001\/jama.2021.18236","volume":"326","author":"VW Skrivankova","year":"2021","unstructured":"Skrivankova, V. W. et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: the strobe-Mr statement. Jama 326, 1614\u20131621 (2021).","journal-title":"Jama"},{"key":"4789_CR21","doi-asserted-by":"publisher","first-page":"e1000412","DOI":"10.1371\/journal.pbio.1000412","volume":"8","author":"C Kilkenny","year":"2010","unstructured":"Kilkenny, C., Browne, W. J., Cuthill, I. C., Emerson, M. & Altman, D. G. Improving bioscience research reporting: the arrive guidelines for reporting animal research. PLoS Biol. 8, e1000412 (2010).","journal-title":"PLoS Biol."},{"key":"4789_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-022-04706-x","volume":"23","author":"EB Fauman","year":"2022","unstructured":"Fauman, E. B. & Hyde, C. An optimal variant to gene distance window derived from an empirical definition of cis and trans protein Qtls. BMC Bioinforma. 23, 169 (2022).","journal-title":"BMC Bioinforma."},{"key":"4789_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1366736","volume":"15","author":"W Zhao","year":"2024","unstructured":"Zhao, W. et al. Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis. Front Immunol. 15, 1366736 (2024).","journal-title":"Front Immunol."},{"key":"4789_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01229-9","volume":"15","author":"J Sun","year":"2023","unstructured":"Sun, J. et al. Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome. Genome Med 15, 75 (2023).","journal-title":"Genome Med"},{"key":"4789_CR25","doi-asserted-by":"crossref","unstructured":"Schmidt, A. F. et al. Genetic drug target validation using Mendelian randomisation. Nat. Commun. 11, 3255 (2020).","DOI":"10.1038\/s41467-020-16969-0"},{"key":"4789_CR26","doi-asserted-by":"publisher","first-page":"D977","DOI":"10.1093\/nar\/gkac1010","volume":"51","author":"E Sollis","year":"2023","unstructured":"Sollis, E. et al. The Nhgri-Ebi Gwas catalog: knowledgebase and deposition resource. Nucleic Acids Res. 51, D977\u2013D985 (2023).","journal-title":"Nucleic Acids Res."},{"key":"4789_CR27","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/s41431-017-0053-7","volume":"26","author":"J Fadista","year":"2018","unstructured":"Fadista, J. et al. Genome-wide association study of hirschsprung disease detects a novel low-frequency variant at the ret Locus. Eur. J. Hum. Genet 26, 561\u2013569 (2018).","journal-title":"Eur. J. Hum. Genet"},{"key":"4789_CR28","doi-asserted-by":"crossref","unstructured":"Liu, W. et al. Association between gut microbiota and hirschsprung disease: a bidirectional two-sample Mendelian randomization study. Front. Microbiol. 15, 1366181 (2024).","DOI":"10.3389\/fmicb.2024.1366181"},{"key":"4789_CR29","doi-asserted-by":"crossref","unstructured":"Hemani, G. et al. The Mr-base platform supports systematic causal inference across the human phenome. Elife 7, e34408 (2018).","DOI":"10.7554\/eLife.34408"},{"key":"4789_CR30","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","volume":"50","author":"M Verbanck","year":"2018","unstructured":"Verbanck, M., Chen, C.-Y., Neale, B. & Do, R. Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases. Nat. Genet. 50, 693\u2013698 (2018).","journal-title":"Nat. Genet."},{"key":"4789_CR31","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/ng.3538","volume":"48","author":"Z Zhu","year":"2016","unstructured":"Zhu, Z. et al. Integration of summary data from Gwas and Eqtl studies predicts complex trait gene targets. Nat. Genet. 48, 481\u2013487 (2016).","journal-title":"Nat. Genet."},{"key":"4789_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03371-0","volume":"9","author":"Y Wu","year":"2018","unstructured":"Wu, Y. et al. Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits. Nat. Commun. 9, 918 (2018).","journal-title":"Nat. Commun."},{"key":"4789_CR33","doi-asserted-by":"publisher","first-page":"9440","DOI":"10.1073\/pnas.1530509100","volume":"100","author":"JD Storey","year":"2003","unstructured":"Storey, J. D. & Tibshirani, R. Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. USA 100, 9440\u20139445 (2003).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"4789_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104494","volume":"89","author":"J Chen","year":"2023","unstructured":"Chen, J. et al. Therapeutic targets for inflammatory bowel disease: proteome-wide mendelian randomization and colocalization analyses. EBioMedicine 89, 104494 (2023).","journal-title":"EBioMedicine"},{"key":"4789_CR35","doi-asserted-by":"publisher","first-page":"D1144","DOI":"10.1093\/nar\/gkaa1084","volume":"49","author":"SL Freshour","year":"2021","unstructured":"Freshour, S. L. et al. Integration of the drug-gene interaction database (Dgidb 4.0) with open crowdsource efforts. Nucleic Acids Res. 49, D1144\u2013D1151 (2021).","journal-title":"Nucleic Acids Res."},{"key":"4789_CR36","doi-asserted-by":"publisher","first-page":"D930","DOI":"10.1093\/nar\/gky1075","volume":"47","author":"D Mendez","year":"2019","unstructured":"Mendez, D. et al. Chembl: towards direct deposition of bioassay data. Nucleic Acids Res 47, D930\u2013D940 (2019).","journal-title":"Nucleic Acids Res"},{"key":"4789_CR37","doi-asserted-by":"publisher","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","volume":"46","author":"DS Wishart","year":"2018","unstructured":"Wishart, D. S. et al. Drugbank 5.0: a major update to the drugbank database for 2018. Nucleic Acids Res. 46, D1074\u2013D1082 (2018).","journal-title":"Nucleic Acids Res."},{"key":"4789_CR38","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.917243","volume":"10","author":"S Bhave","year":"2022","unstructured":"Bhave, S. et al. Ednrb (-\/-) mice with Hirschsprung disease are missing Gad2-expressing enteric neurons in the ganglionated small intestine. Front Cell Dev. Biol. 10, 917243 (2022).","journal-title":"Front Cell Dev. Biol."},{"key":"4789_CR39","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411\u2013420 (2018).","journal-title":"Nat. Biotechnol."},{"key":"4789_CR40","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","volume":"8","author":"SL Wolock","year":"2019","unstructured":"Wolock, S. L., Lopez, R. & Klein, A. M. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 8, 281\u2013291.e289 (2019).","journal-title":"Cell Syst."},{"key":"4789_CR41","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":"4789_CR42","first-page":"383","volume":"99","author":"K Ben Salem","year":"2021","unstructured":"Ben Salem, K. & Ben Abdelaziz, A. Principal component analysis (Pca). Tunis. Med 99, 383\u2013389 (2021).","journal-title":"Tunis. Med"},{"key":"4789_CR43","doi-asserted-by":"crossref","unstructured":"Becht, E. et al. Dimensionality reduction for visualizing single-cell data using Umap. Nat. Biotechnol. 37, 38\u201344 (2018).","DOI":"10.1038\/nbt.4314"},{"key":"4789_CR44","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.jtos.2020.12.004","volume":"20","author":"DQ Li","year":"2021","unstructured":"Li, D. Q. et al. Single-cell transcriptomics identifies limbal stem cell population and cell types mapping its differentiation trajectory in limbal basal epithelium of human cornea. Ocul. Surf. 20, 20\u201332 (2021).","journal-title":"Ocul. Surf."},{"key":"4789_CR45","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s11658-022-00399-5","volume":"27","author":"Z Chen","year":"2022","unstructured":"Chen, Z. et al. X-box binding protein 1 as a key modulator in \u201chealing endothelial cells\u201d, a novel Ec phenotype promoting angiogenesis after Mcao. Cell Mol. Biol. Lett. 27, 97 (2022).","journal-title":"Cell Mol. Biol. Lett."},{"key":"4789_CR46","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.yexcr.2016.12.022","volume":"351","author":"H Yu","year":"2017","unstructured":"Yu, H. et al. Combination of exogenous cell transplantation and 5-Ht(4) receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model. Exp. Cell Res 351, 36\u201342 (2017).","journal-title":"Exp. Cell Res"},{"key":"4789_CR47","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022111139","volume":"42","author":"D Tian","year":"2023","unstructured":"Tian, D. et al. Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by Scfa-induced Mek1\/2 signaling pathway. EMBO J. 42, e111139 (2023).","journal-title":"EMBO J."},{"key":"4789_CR48","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s00439-013-1272-9","volume":"132","author":"H Gui","year":"2013","unstructured":"Gui, H. et al. Ret and Nrg1 interplay in hirschsprung disease. Hum. Genet 132, 591\u2013600 (2013).","journal-title":"Hum. Genet"},{"key":"4789_CR49","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1053\/j.gastro.2018.03.034","volume":"155","author":"Y Sribudiani","year":"2018","unstructured":"Sribudiani, Y. et al. Identification of variants in Ret and Ihh pathway members in a large family with history of Hirschsprung disease. Gastroenterology 155, 118\u2013129.e116 (2018).","journal-title":"Gastroenterology"},{"key":"4789_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ydbio.2013.01.007","volume":"375","author":"FY Hsieh","year":"2013","unstructured":"Hsieh, F. Y. et al. Dner inhibits neural progenitor proliferation and induces neuronal and glial differentiation in Zebrafish. Dev. Biol. 375, 1\u201312 (2013).","journal-title":"Dev. Biol."},{"key":"4789_CR51","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1080\/14734220600632564","volume":"5","author":"SY Saito","year":"2006","unstructured":"Saito, S. Y. & Takeshima, H. Dner as key molecule for cerebellar maturation. Cerebellum 5, 227\u2013231 (2006).","journal-title":"Cerebellum"},{"key":"4789_CR52","first-page":"2357","volume":"17","author":"J Du","year":"2018","unstructured":"Du, J., Wang, X., Zhang, X., Zhang, X. & Jiang, H. Dner modulates the length, polarity and synaptogenesis of spiral ganglion neurons via the notch signaling pathway. Mol. Med Rep. 17, 2357\u20132365 (2018).","journal-title":"Mol. Med Rep."},{"key":"4789_CR53","doi-asserted-by":"publisher","first-page":"25400","DOI":"10.1074\/jbc.M110793200","volume":"277","author":"M Eiraku","year":"2002","unstructured":"Eiraku, M., Hirata, Y., Takeshima, H., Hirano, T. & Kengaku, M. Delta\/Notch-like epidermal growth factor (Egf)-related receptor, a novel Egf-like repeat-containing protein targeted to dendrites of developing and adult central nervous system neurons. J. Biol. Chem. 277, 25400\u201325407 (2002).","journal-title":"J. Biol. Chem."},{"key":"4789_CR54","doi-asserted-by":"publisher","first-page":"6102","DOI":"10.1158\/1078-0432.CCR-20-1587","volume":"26","author":"C Belli","year":"2020","unstructured":"Belli, C. et al. Progresses toward precision medicine in ret-altered solid tumors. Clin. Cancer Res. 26, 6102\u20136111 (2020).","journal-title":"Clin. Cancer Res."},{"key":"4789_CR55","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":"4789_CR56","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13479","volume":"31","author":"JP Russell","year":"2019","unstructured":"Russell, J. P. et al. Enteric ret inhibition attenuates gastrointestinal secretion and motility via cholinergic signaling in rat colonic mucosal preparations. Neurogastroenterol. Motil. 31, e13479 (2019).","journal-title":"Neurogastroenterol. Motil."},{"key":"4789_CR57","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/S0166-2236(97)01154-5","volume":"21","author":"MA Ruegg","year":"1998","unstructured":"Ruegg, M. A. & Bixby, J. L. Agrin orchestrates synaptic differentiation at the vertebrate neuromuscular junction. Trends Neurosci. 21, 22\u201327 (1998).","journal-title":"Trends Neurosci."},{"key":"4789_CR58","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/0955-0674(92)90113-Q","volume":"4","author":"UJ McMahan","year":"1992","unstructured":"McMahan, U. J. et al. Agrin isoforms and their role in synaptogenesis. Curr. Opin. Cell Biol. 4, 869\u2013874 (1992).","journal-title":"Curr. Opin. Cell Biol."},{"key":"4789_CR59","doi-asserted-by":"crossref","unstructured":"Nagy, N. et al. Collagen 18 and Agrin are secreted by neural crest cells to remodel their microenvironment and regulate their migration during enteric nervous system development. Development 145, dev160317 (2018).","DOI":"10.1242\/dev.160317"},{"key":"4789_CR60","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1511-7","volume":"16","author":"J Sanchez-Ventura","year":"2019","unstructured":"Sanchez-Ventura, J., Amo-Aparicio, J., Navarro, X. & Penas, C. Bet protein inhibition regulates cytokine production and promotes neuroprotection after spinal cord injury. J. Neuroinflamm. 16, 124 (2019).","journal-title":"J. Neuroinflamm."},{"key":"4789_CR61","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/nn1492","volume":"8","author":"M Eiraku","year":"2005","unstructured":"Eiraku, M. et al. Dner acts as a neuron-specific notch ligand during Bergmann glial development. Nat. Neurosci. 8, 873\u2013880 (2005).","journal-title":"Nat. Neurosci."},{"key":"4789_CR62","doi-asserted-by":"publisher","first-page":"3467","DOI":"10.1172\/JCI43737","volume":"121","author":"ES Ngan","year":"2011","unstructured":"Ngan, E. S. et al. Hedgehog\/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans. J. Clin. Invest 121, 3467\u20133478 (2011).","journal-title":"J. Clin. Invest"},{"key":"4789_CR63","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1242\/dev.022319","volume":"135","author":"Y Okamura","year":"2008","unstructured":"Okamura, Y. & Saga, Y. Notch signaling is required for the maintenance of enteric neural crest progenitors. Development 135, 3555\u20133565 (2008).","journal-title":"Development"}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-026-04789-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-026-04789-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-026-04789-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T15:02:57Z","timestamp":1772031777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-026-04789-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":63,"alternative-id":["4789"],"URL":"https:\/\/doi.org\/10.1038\/s41390-026-04789-9","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"assertion":[{"value":"29 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 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"}},{"value":"All the animal procedures were handled in accordance with the guidelines outlined by the Animal Care and Ethics Committee of Xi\u2019an Jiaotong University (No. 2018-2148). Clinical trial number with the Clinical Trial Registry: not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}