{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T22:23:13Z","timestamp":1771539793899,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011866","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM147704"],"award-info":[{"award-number":["R35GM147704"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>The gonad of <jats:italic><jats:italic>Caenorhabditis elegans<\/jats:italic><\/jats:italic> hermaphrodites is a longstanding model of cell migration, stem cell niche function, and organogenesis, but it has not yet been investigated using single-cell RNA-sequencing (scRNA-seq). Using a recently published scRNA-seq dataset of adult <jats:italic><jats:italic>C. elegans<\/jats:italic><\/jats:italic> hermaphrodites, we identified a previously unknown regulator of the leader cell of gonad migration (the distal tip cell, or DTC). The gene <jats:italic><jats:italic>mig-21<\/jats:italic><\/jats:italic> is both highly and specifically expressed in the DTC, yet has no known role in that cell. However, <jats:italic><jats:italic>mig-21<\/jats:italic><\/jats:italic> regulates cell migration in other developmental contexts. Using classical genetics techniques, RNAi knockdown, and live cell imaging, we discovered that <jats:italic><jats:italic>mig-21<\/jats:italic><\/jats:italic> acts synergistically with the Wnt and Netrin pathways to guide anteroposterior and dorsoventral phases of migration in the DTC at the level of signaling, not DTC cell structure. Known interactors of <jats:italic><jats:italic>mig-21<\/jats:italic><\/jats:italic> in other cell types\u2013like PTP-3C\u2013also act with MIG-21 in DTC migration. Despite its expression in stationary adult DTCs, <jats:italic><jats:italic>mig-21<\/jats:italic><\/jats:italic> does not play a role in the cessation of DTC migration but instead seems to impart continued sensitivity of the DTC to Wnt and Netrin in adulthood. This study reveals additional complexity of signaling integration between major regulators of germline stem cell niche migration, and as a proof of concept it demonstrates the utility of scRNA-seq datasets in revealing testable hypotheses about genetic networks that were masked by redundancy in traditional screening methods.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011866","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:34:19Z","timestamp":1757957659000},"page":"e1011866","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["MIG-21 interacts with Wnt and Netrin signaling in gonad migration in C. elegans"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3675-8465","authenticated-orcid":true,"given":"Xin","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0967-4020","authenticated-orcid":true,"given":"Kacy Lynn","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"issue":"5","key":"pgen.1011866.ref001","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1261\/rna.078965.121","article-title":"Review of single-cell RNA-seq data clustering for cell-type identification and characterization","volume":"29","author":"S Zhang","year":"2023","journal-title":"RNA"},{"key":"pgen.1011866.ref002","doi-asserted-by":"crossref","DOI":"10.1093\/database\/baaa073","article-title":"A curated database reveals trends in single-cell transcriptomics","volume":"2020","author":"V Svensson","year":"2020","journal-title":"Database (Oxford)"},{"issue":"7718","key":"pgen.1011866.ref003","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41586-018-0394-6","article-title":"A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte","volume":"560","author":"LW Plasschaert","year":"2018","journal-title":"Nature"},{"issue":"25","key":"pgen.1011866.ref004","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adg0506","article-title":"Whole-body gene expression atlas of an adult metazoan","volume":"9","author":"A Ghaddar","year":"2023","journal-title":"Sci Adv"},{"issue":"1","key":"pgen.1011866.ref005","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/(SICI)1097-0177(200005)218:1<2::AID-DVDY2>3.0.CO;2-W","article-title":"TheCaenorhabditis elegans gonad: A test tube for cell and developmental biology","volume":"218","author":"EJA Hubbard","year":"2000","journal-title":"Dev Dyn"},{"issue":"3","key":"pgen.1011866.ref006","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/jdb8030014","article-title":"Recent Advances in the Genetic, Anatomical, and Environmental Regulation of the C. elegans Germ Line Progenitor Zone","volume":"8","author":"K Gordon","year":"2020","journal-title":"J Dev Biol"},{"issue":"4","key":"pgen.1011866.ref007","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/wdev.45","article-title":"Gonad morphogenesis and distal tip cell migration in the Caenorhabditis elegans hermaphrodite","volume":"1","author":"M-C Wong","year":"2012","journal-title":"Wiley Interdiscip Rev Dev Biol"},{"issue":"6","key":"pgen.1011866.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004381","article-title":"Netrins and Wnts function redundantly to regulate antero-posterior and dorso-ventral guidance in C. elegans","volume":"10","author":"N Levy-Strumpf","year":"2014","journal-title":"PLoS Genet"},{"key":"pgen.1011866.ref009","unstructured":"Wormseq \u2013 Single-cell transcriptional atlas of adult C. elegans. https:\/\/wormseq.org\/. 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