{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T23:36:09Z","timestamp":1786750569901,"version":"build-2736575974"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004189","name":"Max Planck Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IMPRS \u201cFrom Molecules to Organisms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nematodes show an extraordinary diversity of mouth structures and strikingly different feeding strategies, which has enabled an invasion of all ecosystems. However, nearly nothing is known about the structural and molecular architecture of the nematode mouth (stoma). Pristionchus pacificus is an intensively studied nematode that exhibits unique life history traits, including predation, teeth-like denticle formation, and mouth-form plasticity. Here, we used a large-scale genetic screen to identify genes involved in mouth formation. We identified Ppa-dpy-6 to encode a Mucin-type hydrogel-forming protein that is macroscopically involved in the specification of the cheilostom, the anterior part of the mouth. We used a recently developed protocol for geometric morphometrics of miniature animals to characterize these defects further and found additional defects that affect mouth form, shape, and size resulting in an overall malformation of the mouth. Additionally, Ppa-dpy-6 is shorter than wild-type with a typical Dumpy phenotype, indicating a role in the formation of the external cuticle. This concomitant phenotype of the cheilostom and cuticle provides the first molecular support for the continuity of these structures and for the separation of the cheilostom from the rest of the stoma. In Caenorhabditis elegans, dpy-6 was an early mapping mutant but its molecular identity was only determined during genome-wide RNAi screens and not further investigated. Strikingly, geometric morphometric analysis revealed previously unrecognized cheilostom and gymnostom defects in Cel-dpy-6 mutants. Thus, the Mucin-type protein DPY-6 represents to the best of our knowledge, the first protein involved in nematode mouth formation with a conserved role in cuticle deposition. This study opens new research avenues to characterize the molecular composition of the nematode mouth, which is associated with extreme ecological diversification.<\/jats:p>","DOI":"10.1093\/genetics\/iyab233","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T14:29:32Z","timestamp":1640269772000},"source":"Crossref","is-referenced-by-count":23,"title":["The oscillating Mucin-type protein DPY-6 has a conserved role in nematode mouth and cuticle formation"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1183-011X","authenticated-orcid":false,"given":"Shuai","family":"Sun","sequence":"first","affiliation":[{"name":"Department for Integrative Evolutionary Biology, Max Planck Institute for Biology T\u00fcbingen,\u00a072076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0920-4427","authenticated-orcid":false,"given":"Tobias","family":"Theska","sequence":"additional","affiliation":[{"name":"Department for Integrative Evolutionary Biology, Max Planck Institute for Biology T\u00fcbingen,\u00a072076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanh","family":"Witte","sequence":"additional","affiliation":[{"name":"Department for Integrative Evolutionary Biology, Max Planck Institute for Biology T\u00fcbingen,\u00a072076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9367-8552","authenticated-orcid":false,"given":"Erik J","family":"Ragsdale","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1503-7749","authenticated-orcid":false,"given":"Ralf J","family":"Sommer","sequence":"additional","affiliation":[{"name":"Department for Integrative Evolutionary Biology, Max Planck Institute for Biology T\u00fcbingen,\u00a072076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"2022030316414908300_iyab233-B1","article-title":"Geomorph: Software for Geometric Morphometric Analyses","author":"Adams","year":"2021"},{"issue":"4","key":"2022030316414908300_iyab233-B2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/2041-210X.12035","article-title":"geomorph: an R package for the collection and analysis of geometric morphometric shape data","volume":"4","author":"Adams","year":"2013","journal-title":"Methods Ecol Evol"},{"issue":"938","key":"2022030316414908300_iyab233-B3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1098\/rstb.1976.0085","article-title":"The pharynx of Caenorhabditis elegans","volume":"275","author":"Albertson","year":"1976","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"1","key":"2022030316414908300_iyab233-B4","first-page":"32","article-title":"A new method for non-parametric multivariate analysis of variance","volume":"26","author":"Anderson","year":"2001","journal-title":"Austral Ecol"},{"key":"2022030316414908300_iyab233-B5","first-page":"1","volume-title":"Wiley Statsref: Statistics Reference Online","author":"Anderson","year":"2014"},{"key":"2022030316414908300_iyab233-B6","doi-asserted-by":"crossref","DOI":"10.1079\/9780851994215.0000","volume-title":"Nematode Parasites of Vertebrates","author":"Anderson","year":"2000"},{"issue":"3","key":"2022030316414908300_iyab233-B7","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1139\/z97-051","article-title":"The buccal capsule of Aduncospiculum halicti (Nematoda: Diplogastridae): an ultrastructural and molecular phylogenetic study","volume":"75","author":"Baldwin","year":"1997","journal-title":"Can J Zool"},{"issue":"7305","key":"2022030316414908300_iyab233-B8","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/nature09164","article-title":"Co-option of the endocrine signaling module dafachronic acid-DAF-12 in nematode evolution","volume":"466","author":"Bento","year":"2010","journal-title":"Nature"},{"issue":"1","key":"2022030316414908300_iyab233-B9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","article-title":"The genetics of Caenorhabditis elegans","volume":"77","author":"Brenner","year":"1974","journal-title":"Genetics"},{"issue":"11","key":"2022030316414908300_iyab233-B10","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1093\/molbev\/msz171","article-title":"Multiple plasticity regulators reveal targets specifying an induced predatory form in nematodes","volume":"36","author":"Bui","year":"2019","journal-title":"Mol. Biol. Evol"},{"issue":"9","key":"2022030316414908300_iyab233-B11","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1002\/jmor.20567","article-title":"The nematode stoma: homology of cell architecture with improved understanding by confocal microscopy of labeled boundaries","volume":"277","author":"Burr","year":"2016","journal-title":"J Morphol"},{"issue":"2","key":"2022030316414908300_iyab233-B12","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/molbev\/msaa235","article-title":"Polyphenism of a novel trait integrated rapidly evolving genes into ancestrally plastic networks","volume":"38","author":"Casasa","year":"2021","journal-title":"Mol Biol Evol"},{"issue":"4","key":"2022030316414908300_iyab233-B13","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3390\/jdb8040023","article-title":"C. elegans apical extracellular matrix shape epithelia","volume":"8","author":"Cohen","year":"2020","journal-title":"J Dev Biol"},{"issue":"4","key":"2022030316414908300_iyab233-B14","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/hdy.2014.75","article-title":"A method for analysis of phenotypic change for phenotypes described by high-dimensional data","volume":"115","author":"Collyer","year":"2015","journal-title":"Heredity (Edinb)"},{"issue":"7","key":"2022030316414908300_iyab233-B15","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1111\/2041-210X.13029","article-title":"RRPP: an R package for fitting linear models to high-dimensional data using residual randomization","volume":"9","author":"Collyer","year":"2018","journal-title":"Methods Ecol Evol"},{"key":"2022030316414908300_iyab233-B16","author":"Collyer","year":"2021"},{"issue":"1\u20134","key":"2022030316414908300_iyab233-B17","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1163\/003925995X00143","article-title":"Ultrastructure of the stoma in Cephalobidae, Panagrolaimidae and Rhabditidae, with a proposal for a revised stoma terminology in Rhabditida (Nematoda)","volume":"41","author":"De Ley","year":"1995","journal-title":"Nematologica"},{"issue":"10","key":"2022030316414908300_iyab233-B18","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1038\/ng.227","article-title":"The Pristionchus pacificus genome provides a unique perspective on nematode lifestyle and parasitism","volume":"40","author":"Dieterich","year":"2008","journal-title":"Nat Genet"},{"key":"2022030316414908300_iyab233-B19","author":"Fraley","year":"2021"},{"issue":"1","key":"2022030316414908300_iyab233-B20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1046\/j.1439-0469.2000.381125.x","article-title":"Comparative and functional morphology of the buccal cavity of Diplogastridae (Nematoda) and a first outline of the phylogeny of this taxon","volume":"38","author":"F\u00fcrst von Lieven","year":"2000","journal-title":"J Zool. Syst."},{"key":"2022030316414908300_iyab233-B21","volume-title":"C. elegans Atlas","author":"Hall","year":"2008"},{"issue":"4","key":"2022030316414908300_iyab233-B22","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1534\/genetics.120.303785","article-title":"Improving trangenesis efficiency and CRISPR-associated tools through codon optimization and native intron addition in nematodes","volume":"216","author":"Han","year":"2020","journal-title":"Genetics"},{"key":"2022030316414908300_iyab233-B23","article-title":"Comparative reconstruction of the predatory feeding structure of the polyphonic nematode Pristionchus pacificus","author":"Harry","year":"2021","journal-title":"bioRxiv"},{"issue":"3","key":"2022030316414908300_iyab233-B24","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/gene.20084","article-title":"Mutations with altered gross-morphology in the nematode Pristionchus pacificus","volume":"40","author":"Kenning","year":"2004","journal-title":"Genesis"},{"key":"2022030316414908300_iyab233-B25","doi-asserted-by":"crossref","DOI":"10.1201\/b12614","volume-title":"The Biology of Nematodes","author":"Lee","year":"2002"},{"issue":"14","key":"2022030316414908300_iyab233-B26","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"16","key":"2022030316414908300_iyab233-B27","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"12","key":"2022030316414908300_iyab233-B28","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2022030316414908300_iyab233-B29","volume-title":"Nematodes","author":"Malakhov","year":"1994"},{"key":"2022030316414908300_iyab233-B30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15252\/msb.20209498","article-title":"Developmental function and state transitions of a gene expression oscillator in Caenorhabditis elegans","volume":"16","author":"Meeuse","year":"2020","journal-title":"Mol. Syst. Biol"},{"issue":"6","key":"2022030316414908300_iyab233-B31","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.jhevol.2004.03.006","article-title":"Comparison of cranial ontogenetic trajectories among great apes and humans","volume":"46","author":"Mitteroecker","year":"2004","journal-title":"J Hum Evol"},{"key":"2022030316414908300_iyab233-B32","first-page":"59","article-title":"A brief review of shape, form, and allometry in geometric morphometrics, with applications to human facial morphology","volume":"24","author":"Mitteroecker","year":"2013","journal-title":"HYSTRIX"},{"key":"2022030316414908300_iyab233-B33","author":"M\u00fcller","year":"2010"},{"issue":"3","key":"2022030316414908300_iyab233-B34","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00427-020-00651-y","article-title":"Screening for CRISPR\/Cas9-induced mutations using a co-injection marker in the nematode Pristionchus pacificus","volume":"230","author":"Nakayama","year":"2020","journal-title":"Dev Genes Evol"},{"issue":"2","key":"2022030316414908300_iyab233-B35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ijpddr.2014.05.003","article-title":"Enzymology of the nematode cuticle: a potential drug target?","volume":"4","author":"Page","year":"2014","journal-title":"Int J Parasitol Drugs Drug Resist"},{"issue":"11","key":"2022030316414908300_iyab233-B36","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1111\/mpp.12704","article-title":"Knockdown of a mucin-like gene in Meloidogyne incognita (Nematoda) decreases attachment of endospores of Pasteuria penetrans to the infective juveniles and reduces nematode fecundity","volume":"19","author":"Phani","year":"2018","journal-title":"Mol Plant Pathol"},{"key":"2022030316414908300_iyab233-B37","doi-asserted-by":"crossref","DOI":"10.1080\/01677063.2020.1833004","article-title":"Intraguild predation between Pristionchus pacificus and Caenorhabditis elegans: a complex interaction with the potential for aggressive behavior","author":"Quach","year":"2020","journal-title":"J Neurogenetics"},{"issue":"8","key":"2022030316414908300_iyab233-B38","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.ijpara.2012.05.005","article-title":"The importance of being regular: Caenorhabditis elegans and Pristionchus pacificus defecation mutants are hypersusceptible to bacterial pathogens","volume":"42","author":"Rae","year":"2012","journal-title":"Int J Parasitol"},{"issue":"1686","key":"2022030316414908300_iyab233-B39","first-page":"1299","article-title":"Resolving phylogenetic incongruence to articulate homology and phenotypic evolution: a case study from Nematoda","volume":"277","author":"Ragsdale","year":"2010","journal-title":"Proc Biol Sci"},{"issue":"4","key":"2022030316414908300_iyab233-B40","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.cell.2013.09.054","article-title":"A developmental switch coupled to the evolution of plasticity acts through a sulfatase","volume":"155","author":"Ragsdale","year":"2013","journal-title":"Cell"},{"key":"2022030316414908300_iyab233-B41","year":"2021"},{"issue":"3","key":"2022030316414908300_iyab233-B42","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.celrep.2017.09.077","article-title":"Single-molecule sequencing reveals the chromosome-scale genomic architecture of the nematode model organism Pristionchus pacificus","volume":"21","author":"R\u00f6delsperger","year":"2017","journal-title":"Cell Rep"},{"issue":"7","key":"2022030316414908300_iyab233-B43","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"2022030316414908300_iyab233-B44","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/B978-0-12-810493-4.00011-0","volume-title":"Statistical Shape and Deformation Analysis","author":"Schlager","year":"2017"},{"key":"2022030316414908300_iyab233-B45","author":"Schlager","year":"2021"},{"issue":"10","key":"2022030316414908300_iyab233-B47","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1016\/j.celrep.2018.05.008","article-title":"A developmental switch regulating phenotypic plasticity is a part of a conserved multi-gene locus","volume":"23","author":"Sieriebriennikov","year":"2018","journal-title":"Cell Rep"},{"issue":"4","key":"2022030316414908300_iyab233-B48","doi-asserted-by":"crossref","first-page":"e1008687","DOI":"10.1371\/journal.pgen.1008687","article-title":"Conserved hormone-receptors controlling a novel plastic trait target fast-evolving genes expressed in a single cell","volume":"16","author":"Sieriebriennikov","year":"2020","journal-title":"PLoS Genet"},{"issue":"1","key":"2022030316414908300_iyab233-B49","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1371\/journal.pbio.0000012","article-title":"Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions","volume":"1","author":"Simmer","year":"2003","journal-title":"PLoS Biol"},{"issue":"1","key":"2022030316414908300_iyab233-B50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1534\/genetics.120.303163","article-title":"Phenotypic plasticity: from theory and genetics to current and future challenges","volume":"215","author":"Sommer","year":"2020","journal-title":"Genetics"},{"key":"2022030316414908300_iyab233-B51","first-page":"511","article-title":"Morphological, genetic and molecular description of Pristionchus pacificus sp. n. (Nematoda, Diplogastridae)","volume":"19","author":"Sommer","year":"1996","journal-title":"Fundam. Appl. Nematol"},{"issue":"9","key":"2022030316414908300_iyab233-B52","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1101\/gr.275303.121","article-title":"Single worm transcriptomics identifies a developmental core network of oscillating genes with deep conservation across nematodes","volume":"31","author":"Sun","year":"2021","journal-title":"Genome Res"},{"key":"2022030316414908300_iyab233-B53","doi-asserted-by":"crossref","first-page":"e05463","DOI":"10.7554\/eLife.05463","article-title":"Rapid diversification associated with a macroevolutionary pulse of developmental plasticity","volume":"4","author":"Susoy","year":"2015","journal-title":"eLIFE"},{"issue":"8","key":"2022030316414908300_iyab233-B54","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1038\/s41596-020-0347-z","article-title":"Geometric morphometrics of microscopic animals as exemplified by model nematodes","volume":"15","author":"Theska","year":"2020","journal-title":"Nat Protoc"},{"issue":"7768","key":"2022030316414908300_iyab233-B55","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41586-019-1418-6","article-title":"A global database of sol nematodes abundance and functional group composition","volume":"572","author":"van den Hoogen","year":"2019","journal-title":"Nature"},{"key":"2022030316414908300_iyab233-B56","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev-cellbio-100617-062818","article-title":"Mucins and their role in shaping the function of mucus barriers","volume":"34","author":"Wagner","year":"2018","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"2","key":"2022030316414908300_iyab233-B57","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/s41578-018-0079-7","article-title":"Engineering mucus to study and influence the microbiome","volume":"4","author":"Werlang","year":"2019","journal-title":"Nat Rev Mater"},{"issue":"1","key":"2022030316414908300_iyab233-B58","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1038\/s41598-017-07455-7","article-title":"Environmental influence on Pristionchus pacificus mouth-form through different culture methods","volume":"7","author":"Werner","year":"2017","journal-title":"Sci Rep"},{"issue":"24","key":"2022030316414908300_iyab233-B59","doi-asserted-by":"crossref","first-page":"8080","DOI":"10.1039\/C6NR09736G","article-title":"The particle in the spide\u0155s web: transport through biological hydrogels","volume":"9","author":"Witten","year":"2017","journal-title":"Nanoscale"},{"key":"2022030316414908300_iyab233-B60","first-page":"71","volume-title":"The Organization of Nematodes","author":"Wright","year":"1976"},{"issue":"10","key":"2022030316414908300_iyab233-B61","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1139\/z81-266","article-title":"The buccal capsule of Caenorhabditis elegans (Nematoda: Rhabditidae): an ultrastructural study","volume":"59","author":"Wright","year":"1981","journal-title":"Can J Zool"}],"container-title":["Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/genetics\/advance-article-pdf\/doi\/10.1093\/genetics\/iyab233\/42535908\/iyab233.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/genetics\/article-pdf\/220\/3\/iyab233\/42691479\/iyab233.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/genetics\/article-pdf\/220\/3\/iyab233\/42691479\/iyab233.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T06:55:45Z","timestamp":1674197745000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/genetics\/article\/doi\/10.1093\/genetics\/iyab233\/6481560"}},"subtitle":[],"editor":[{"given":"B","family":"Grant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":60,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,12,23]]},"published-print":{"date-parts":[[2022,3,3]]}},"URL":"https:\/\/doi.org\/10.1093\/genetics\/iyab233","relation":{},"ISSN":["1943-2631"],"issn-type":[{"value":"1943-2631","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,3,1]]},"published":{"date-parts":[[2021,12,23]]},"article-number":"iyab233"}}