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It has been hypothesized that signal transmission via neuropeptides played a crucial role in the regulation of nervous systems in the bilaterian ancestor. Identification, expression and functional analyses of neuropeptides and their receptors across different taxonomic groups are important for better understanding the origin(s) of bilaterian neuropeptide signalling. An example is flatworms belonging to the Platyhelminthes (spiralian protostomes) and Xenacoelomorpha (sister to all Bilateria or sister to Ambulacraria). Despite their simple morphology (i.e., a body plan lacking a coelom and circulatory system), they often possess brain\u2010like central nervous systems and a number of bilaterian\u2010conserved neuropeptides. This feature makes them useful models for analyses of neuropeptides and their links to nervous systems. Although previous studies have revealed orthologous relationships between vertebrate neuropeptides and those found in both marine Platyhelminthes and Xenacoelomorpha, our work suggests possible ancestral functions of vasopressin\/oxytocin (VP\/OT) peptides (platytocin) in these groups: (1) Platytocin exhibits conserved functions of antidiuresis and reproduction across Bilateria; (2) Several ancient neuropeptide families, including VP\/OT and gonadotropin\u2010releasing hormone (GnRH)\/corazonin, are conserved across phylogenetically distant flatworms, while overall repertoires show a mosaic pattern of conservation and lineage\u2010specific diversification. These findings suggest that core bilaterian signalling systems were established early, with subsequent lineage\u2010specific diversification, and highlight the importance of comparative studies across multiple species from different superphyla to understand the principles of neuropeptide signalling.<\/jats:p>","DOI":"10.1111\/jne.70259","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:36:52Z","timestamp":1788860212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Marine flatworms as windows into the evolution of bilaterian neuropeptide signalling"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0761-0704","authenticated-orcid":false,"given":"Ryo","family":"Nakamura","sequence":"first","affiliation":[{"name":"Ushimado Marine Institute, Faculty of Science Okayama University  Okayama 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Ushimado Marine Institute, Faculty of Science Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2019.02.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.193342"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1221833110"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msac051"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobeha.2024.101456"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2019.0761"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06964"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.02.016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13127\u2010012\u20100112\u20104"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2142\/biophysico.bppb\u2010v21.s012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13064\u2010024\u201000187\u20101"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2108\/zs230082"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1590\/s1415\u2010475738320150013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00427\u2010010\u20100328\u20102"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.94948"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2022.10.036"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.04.009"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16520"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abk0331"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742\u20109994\u20109\u201027"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg6034"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msy160"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe2741"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915\u2010024\u201002017\u20106"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e34473"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1387176"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msab211"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2017.01.004"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201040949\u20100"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2011.01.005"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201014\u2010906"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24289"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220285110"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219956110"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.06.052"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800274R"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2010.02.010"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201015\u2010840"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010015\u20101510\u20108"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaq1736"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaq1723"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010018\u20101498\u2010x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.09.056"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1817788116"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.01.034"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1226860"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1226201"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep14469"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097\u2010010x(19961001)276:2<151::Aid\u2010jez8>3.0.Co;2\u2010n"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2008.04.006"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/359233a0"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.110379"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2020.1198"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"1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