{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:25:42Z","timestamp":1767180342949,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011944","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000}}],"reference-count":106,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005945","name":"Hirosaki University","doi-asserted-by":"publisher","award":["Hirosaki University Institutional Research Grant for Future Innovation"],"award-info":[{"award-number":["Hirosaki University Institutional Research Grant for Future Innovation"]}],"id":[{"id":"10.13039\/501100005945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H01249"],"award-info":[{"award-number":["16H01249"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H03256"],"award-info":[{"award-number":["19H03256"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H05236"],"award-info":[{"award-number":["19H05236"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K02303"],"award-info":[{"award-number":["25K02303"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Many metazoans switch between asexual and sexual reproduction based on environmental changes, life cycle phases, or both. This reproductive strategy enables them to benefit from the features of both reproductive modes. In general, asexual reproduction is broadly divided into parthenogenesis and vegetative reproduction. As in parthenogenesis, individuals develop ovaries and lay eggs, the most significant event in switching from parthenogenesis to sexual reproduction is the production of testes. Meanwhile, in vegetative reproduction, individuals do not need germ cells themselves. Thus, they must post-embryonically develop and maintain germ cells derived from pluripotent cells as they switch from vegetative to sexual reproduction. The complicated mechanisms for controlling the postembryonic reproductive development remain unknown. The planarian\n                    <jats:italic>Dugesia ryukyuensis<\/jats:italic>\n                    can switch from vegetative to sexual reproduction by stimulating bioactive compounds called sex-inducing substances, which are widely conserved in Platyhelminthes, including parasitic flatworms. The two reproductive modes are facilitated by the presence of adult pluripotent stem cells, which generate any type of somatic tissue in the asexual state and produce and maintain hermaphroditic reproductive organs in the sexual state. In this study, using RNA sequencing analysis in experimental sexualization by sex-inducing substances, we identified four essential genes for sexualization. A common feature following the knockdown of the four essential genes was a blockage of testicular differentiation. One of the four essential genes was a gap junction gene,\n                    <jats:italic>Dr-siri<\/jats:italic>\n                    (\n                    <jats:italic>\n                      <jats:underline>D<\/jats:underline>\n                      ugesia\n                      <jats:underline>r<\/jats:underline>\n                      yukyuensis\n                    <\/jats:italic>\n                    -\n                    <jats:underline>s<\/jats:underline>\n                    exual\n                    <jats:underline>i<\/jats:underline>\n                    nduction-\n                    <jats:underline>r<\/jats:underline>\n                    elated\n                    <jats:underline>i<\/jats:underline>\n                    nnexin). We suggest that the establishment of a testicular stem cell niche supported by Dr-siri protein is responsible for the breakthrough of dormancy in postembryonic reproductive development in planarian reproductive switching. Our findings suggest that the production of testes might be crucial for even switching from vegetative to sexual reproduction.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1011944","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T18:35:15Z","timestamp":1763490915000},"page":"e1011944","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of an innexin required for termination of the asexual state in planarian reproductive switching"],"prefix":"10.1371","volume":"21","author":[{"given":"Nobuyoshi","family":"Kumagai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michio","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tosei","family":"Hanai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Hino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8178-3574","authenticated-orcid":true,"given":"Shunta","family":"Yorimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Manta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuzo","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moe","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"Tajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riku","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hikaru","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kota","family":"Miura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Kashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsushi","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Shigenobu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0020-6231","authenticated-orcid":true,"given":"Ryohei","family":"Furukawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-2129","authenticated-orcid":true,"given":"Kiyono","family":"Sekii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5839-0337","authenticated-orcid":true,"given":"Kazuya","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"pgen.1011944.ref001","volume-title":"Adaptation and natural selection","author":"G Williams","year":"1966"},{"issue":"5","key":"pgen.1011944.ref002","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0019639","article-title":"New insights into placozoan sexual reproduction and development","volume":"6","author":"M Eitel","year":"2011","journal-title":"PLoS One"},{"issue":"1","key":"pgen.1011944.ref003","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1080\/19420889.2020.1838809","article-title":"Why isn\u2019t sex optional? Stem-cell competition, loss of regenerative capacity, and cancer in metazoan evolution","volume":"13","author":"C Fields","year":"2020","journal-title":"Commun Integr Biol"},{"key":"pgen.1011944.ref004","doi-asserted-by":"crossref","first-page":"203846","DOI":"10.1016\/j.cdev.2023.203846","article-title":"The Hydra stem cell system - Revisited","volume":"174","author":"TW Holstein","year":"2023","journal-title":"Cells Dev"},{"issue":"1","key":"pgen.1011944.ref005","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13227-021-00185-y","article-title":"Whole body regeneration and developmental competition in two botryllid ascidians","volume":"12","author":"S Nourizadeh","year":"2021","journal-title":"Evodevo"},{"issue":"10","key":"pgen.1011944.ref006","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.cub.2006.04.036","article-title":"Early segregation of germ and somatic lineages during gonadal regeneration in the annelid Enchytraeus japonensis","volume":"16","author":"R Tadokoro","year":"2006","journal-title":"Curr Biol"},{"issue":"1","key":"pgen.1011944.ref007","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1440-169X.2009.01149.x","article-title":"Stem cell system in asexual and sexual reproduction of Enchytraeus japonensis (Oligochaeta, Annelida)","volume":"52","author":"C Yoshida-Noro","year":"2010","journal-title":"Dev Growth Differ"},{"key":"pgen.1011944.ref008","volume-title":"The Masterpiece of Nature","author":"G Bell","year":"1982"},{"issue":"5","key":"pgen.1011944.ref009","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/BF02143204","article-title":"Developmental genes as a potential tool in population ecology of complex animal life cycles?","volume":"51","author":"B Schierwater","year":"1995","journal-title":"Experientia"},{"issue":"9","key":"pgen.1011944.ref010","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/nbt1331","article-title":"High-frequency generation of viable mice from engineered bi-maternal embryos","volume":"25","author":"M Kawahara","year":"2007","journal-title":"Nat Biotechnol"},{"issue":"6985","key":"pgen.1011944.ref011","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature02402","article-title":"Birth of parthenogenetic mice that can develop to adulthood","volume":"428","author":"T Kono","year":"2004","journal-title":"Nature"},{"issue":"5880","key":"pgen.1011944.ref012","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1126\/science.1156407","article-title":"Massive horizontal gene transfer in bdelloid rotifers","volume":"320","author":"EA Gladyshev","year":"2008","journal-title":"Science"},{"issue":"5469","key":"pgen.1011944.ref013","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1126\/science.288.5469.1211","article-title":"Evidence for the evolution of bdelloid rotifers without sexual reproduction or genetic exchange","volume":"288","author":"D Mark Welch","year":"2000","journal-title":"Science"},{"issue":"6","key":"pgen.1011944.ref014","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1073\/pnas.0307677100","article-title":"Cytogenetic evidence for asexual evolution of bdelloid rotifers","volume":"101","author":"JL Mark Welch","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pgen.1011944.ref015","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/icb\/33.3.365","article-title":"The Role of Juvenile Hormones in Crustacean Reproduction","volume":"33","author":"H Laufer","year":"1993","journal-title":"Am Zool"},{"issue":"8","key":"pgen.1011944.ref016","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.chemosphere.2005.02.075","article-title":"Production of male neonates in Daphnia magna (Cladocera, Crustacea) exposed to juvenile hormones and their analogs","volume":"61","author":"S Oda","year":"2005","journal-title":"Chemosphere"},{"issue":"1","key":"pgen.1011944.ref017","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.chemosphere.2004.12.080","article-title":"Production of male neonates in four cladoceran species exposed to a juvenile hormone analog, fenoxycarb","volume":"60","author":"S Oda","year":"2005","journal-title":"Chemosphere"},{"issue":"8","key":"pgen.1011944.ref018","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S0045-6535(03)00761-6","article-title":"Juvenile hormone agonists affect the occurrence of male Daphnia","volume":"53","author":"N Tatarazako","year":"2003","journal-title":"Chemosphere"},{"issue":"5","key":"pgen.1011944.ref019","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/jat.2922","article-title":"Molecular impact of juvenile hormone agonists on neonatal Daphnia magna","volume":"34","author":"K Toyota","year":"2014","journal-title":"J Appl Toxicol"},{"issue":"3","key":"pgen.1011944.ref020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1001345","article-title":"Environmental sex determination in the branchiopod crustacean Daphnia magna: deep conservation of a Doublesex gene in the sex-determining pathway","volume":"7","author":"Y Kato","year":"2011","journal-title":"PLoS Genet"},{"issue":"5","key":"pgen.1011944.ref021","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.tcb.2011.01.005","article-title":"Planarian stem cells: a simple paradigm for regeneration","volume":"21","author":"AA Aboobaker","year":"2011","journal-title":"Trends Cell Biol"},{"issue":"1","key":"pgen.1011944.ref022","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1242\/dev.107.1.77","article-title":"Regeneration and pattern formation in planarians: III. Evidence that neoblasts are totipotent stem cells and the source of blastema cells","volume":"107","author":"J Bagu\u00f1\u00e0","year":"1989","journal-title":"Development"},{"key":"pgen.1011944.ref023","first-page":"781","article-title":"Regeneration and pattern formation in planarians: cells, molecules and genes","volume":"11","author":"J Bagu\u00f1\u00e1","year":"1994","journal-title":"Zool Sci"},{"issue":"4","key":"pgen.1011944.ref024","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/09553006814551221","article-title":"Studies on the cellular basis of radiation lethality. 3. The measurement of stem-cell repopulation probability","volume":"14","author":"CS Lange","year":"1968","journal-title":"Int J Radiat Biol Relat Stud Phys Chem Med"},{"issue":"2","key":"pgen.1011944.ref025","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1006\/dbio.2000.9645","article-title":"Bromodeoxyuridine specifically labels the regenerative stem cells of planarians","volume":"220","author":"PA Newmark","year":"2000","journal-title":"Dev Biol"},{"key":"pgen.1011944.ref026","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1387\/ijdb.113434ns","article-title":"Comprehensive gene expression analyses in pluripotent stem cells of a planarian, Dugesia japonica","volume":"56","author":"N Shibata","year":"2012","journal-title":"Int J Dev Biol"},{"issue":"2","key":"pgen.1011944.ref027","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.ydbio.2010.06.017","article-title":"Planarian regeneration involves distinct stem cell responses to wounds and tissue absence","volume":"344","author":"D Wenemoser","year":"2010","journal-title":"Dev Biol"},{"issue":"7","key":"pgen.1011944.ref028","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2018.05.006","article-title":"Prospectively Isolated Tetraspanin+ Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration","volume":"173","author":"A Zeng","year":"2018","journal-title":"Cell"},{"issue":"1","key":"pgen.1011944.ref029","doi-asserted-by":"crossref","first-page":"6706","DOI":"10.1038\/s41467-021-26986-2","article-title":"Hox genes regulate asexual reproductive behavior and tissue segmentation in adult animals","volume":"12","author":"CP Arnold","year":"2021","journal-title":"Nat Commun"},{"issue":"3879","key":"pgen.1011944.ref030","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1126\/science.164.3879.565","article-title":"Fissioning in planarians: control by the brain","volume":"164","author":"JB Best","year":"1969","journal-title":"Science"},{"issue":"1","key":"pgen.1011944.ref031","doi-asserted-by":"crossref","DOI":"10.1088\/1478-3975\/ac2f29","article-title":"Let it rip: the mechanics of self-bisection in asexual planarians determines their population reproductive strategies","volume":"19","author":"T Goel","year":"2021","journal-title":"Phys Biol"},{"issue":"41","key":"pgen.1011944.ref032","doi-asserted-by":"crossref","first-page":"10888","DOI":"10.1073\/pnas.1700762114","article-title":"Mechanics dictate where and how freshwater planarians fission","volume":"114","author":"PT Malinowski","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1011944.ref033","first-page":"515","article-title":"The life history, the normal fission and the reproductive organs of Planaria maculata","volume":"30","author":"WC Curtis","year":"1902","journal-title":"Proc Boston Soc Nat Hist"},{"issue":"2","key":"pgen.1011944.ref034","first-page":"407","article-title":"Stimulation of germ cell proliferation in the planarian Dugesia tigrina (Girard)","volume":"23","author":"C Vowinckel","year":"1970","journal-title":"J Embryol Exp Morphol"},{"issue":"3","key":"pgen.1011944.ref035","first-page":"599","article-title":"Reproduction of Dugesia tigrina under short-day and long-day conditions at different temperatures. II. Asexually derived individuals","volume":"26","author":"C Vowinckel","year":"1971","journal-title":"J Embryol Exp Morphol"},{"issue":"3","key":"pgen.1011944.ref036","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1242\/dev.26.3.587","article-title":"Reproduction of Dugesia tigrina under short-day and long-day conditions at different temperatures","volume":"26","author":"C Vowinckel","year":"1971","journal-title":"Development"},{"key":"pgen.1011944.ref037","first-page":"9","article-title":"Comparative research on the sexualization of fissiparous planarians treated with substances contained in sexual planarians","volume":"11","author":"M Benazzi","year":"1977","journal-title":"Ita J Zool"},{"issue":"2","key":"pgen.1011944.ref038","first-page":"317","article-title":"Genetic and physiologic control of fissioning and sexuality in planarians","volume":"30","author":"M Grasso","year":"1973","journal-title":"J Embryol Exp Morphol"},{"issue":"3","key":"pgen.1011944.ref039","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/S0022-5320(75)80078-5","article-title":"Studies on the role of neurosecretion in the induction of sexuality in a planarian agamic strain","volume":"52","author":"M Grasso","year":"1975","journal-title":"J Ultrastruct Res"},{"issue":"1","key":"pgen.1011944.ref040","first-page":"111","article-title":"Sexualization of Dugesia anderlani by feeding","volume":"9","author":"J Hauser","year":"1987","journal-title":"Acta biologica leopoldensia"},{"issue":"2","key":"pgen.1011944.ref041","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2108\/zsj.16.291","article-title":"Switching from Asexual to Sexual Reproduction in the Planarian Dugesia ryukyuensis: Bioassay System and Basic Description of Sexualizing Process","volume":"16","author":"K Kobayashi","year":"1999","journal-title":"Zoological Science"},{"key":"pgen.1011944.ref042","first-page":"103","article-title":"Sexual induction by feeding in an asexual strain of the fresh-water planarian, Dugesia japonica japonica","volume":"54","author":"T Sakurai","year":"1981","journal-title":"Annot Zool Jap"},{"issue":"1","key":"pgen.1011944.ref043","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/BF00046250","article-title":"On the origin of neoblasts in freshwater planarians (Turbellaria)","volume":"132","author":"W Teshirogi","year":"1986","journal-title":"Hydrobiologia"},{"issue":"1","key":"pgen.1011944.ref044","doi-asserted-by":"crossref","first-page":"105776","DOI":"10.1016\/j.isci.2022.105776","article-title":"Sex-inducing effects toward planarians widely present among parasitic flatworms","volume":"26","author":"K Sekii","year":"2023","journal-title":"iScience"},{"issue":"6","key":"pgen.1011944.ref045","doi-asserted-by":"crossref","first-page":"544","DOI":"10.2108\/zs210029","article-title":"Sex-Inducing Activities of the Land Planarian Bipalium nobile Extract Fractions, Obtained Using Bioassay-Guided Fractionation, in the Freshwater Planarian Dugesia ryukyuensis","volume":"38","author":"M Kitamura","year":"2021","journal-title":"Zoolog Sci"},{"key":"pgen.1011944.ref046","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1742-9994-8-23","article-title":"Sex-inducing effect of a hydrophilic fraction on reproductive switching in the planarian Dugesia ryukyuensis (Seriata, Tricladida)","volume":"8","author":"K Kobayashi","year":"2011","journal-title":"Front Zool"},{"issue":"1","key":"pgen.1011944.ref047","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.1038\/s41598-019-42025-z","article-title":"Transcriptomic analysis reveals differences in the regulation of amino acid metabolism in asexual and sexual planarians","volume":"9","author":"K Sekii","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"pgen.1011944.ref048","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2108\/zsj.24.31","article-title":"The Dugesia ryukyuensis database as a molecular resource for studying switching of the reproductive system","volume":"24","author":"H Ishizuka","year":"2007","journal-title":"Zoolog Sci"},{"issue":"2","key":"pgen.1011944.ref049","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00441-021-03506-8","article-title":"Identification of novel yolk ferritins unique to planarians: planarians supply aluminum rather than iron to vitellaria in egg capsules","volume":"386","author":"O Kawase","year":"2021","journal-title":"Cell Tissue Res"},{"key":"pgen.1011944.ref050","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1038\/ncomms2811","article-title":"A sex-specific transcription factor controls male identity in a simultaneous hermaphrodite","volume":"4","author":"T Chong","year":"2013","journal-title":"Nat Commun"},{"issue":"1","key":"pgen.1011944.ref051","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ydbio.2014.09.024","article-title":"A lophotrochozoan-specific nuclear hormone receptor is required for reproductive system development in the planarian","volume":"396","author":"ME Tharp","year":"2014","journal-title":"Dev Biol"},{"issue":"7","key":"pgen.1011944.ref052","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3001472","article-title":"A Kr\u00fcppel-like factor is required for development and regeneration of germline and yolk cells from somatic stem cells in planarians","volume":"20","author":"M Issigonis","year":"2022","journal-title":"PLoS Biol"},{"issue":"1","key":"pgen.1011944.ref053","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ydbio.2011.10.014","article-title":"Drpiwi-1 is essential for germline cell formation during sexualization of the planarian Dugesia ryukyuensis","volume":"361","author":"H Nakagawa","year":"2012","journal-title":"Dev Biol"},{"issue":"12","key":"pgen.1011944.ref054","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00427-002-0288-2","article-title":"Transcriptional pattern of a novel gene, expressed specifically after the point-of-no-return during sexualization, in planaria","volume":"212","author":"S Hase","year":"2003","journal-title":"Dev Genes Evol"},{"key":"pgen.1011944.ref055","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1387\/ijdb.113433hn","article-title":"The Dr-nanos gene is essential for germ cell specification in the planarian Dugesia ryukyuensis","volume":"56","author":"H Nakagawa","year":"2012","journal-title":"Int J Dev Biol"},{"issue":"18","key":"pgen.1011944.ref056","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1101\/gad.1951010","article-title":"A functional genomic screen in planarians identifies novel regulators of germ cell development","volume":"24","author":"Y Wang","year":"2010","journal-title":"Genes Dev"},{"issue":"15","key":"pgen.1011944.ref057","first-page":"2598","article-title":"Bi-directional gap junction-mediated soma-germline communication is essential for spermatogenesis","volume":"142","author":"CM Smendziuk","year":"2015","journal-title":"Development"},{"issue":"5","key":"pgen.1011944.ref058","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.chembiol.2005.02.013","article-title":"Intercellular communication: the Drosophila innexin multiprotein family of gap junction proteins","volume":"12","author":"R Bauer","year":"2005","journal-title":"Chem Biol"},{"issue":"2","key":"pgen.1011944.ref059","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3390\/ijms21020485","article-title":"Calmodulin-Mediated Regulation of Gap Junction Channels","volume":"21","author":"C Peracchia","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"9","key":"pgen.1011944.ref060","article-title":"Gap junctions mediate discrete regulatory steps during fly spermatogenesis","volume":"18","author":"Y-Y Pesch","year":"2022","journal-title":"PLoS Genet"},{"key":"pgen.1011944.ref061","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.pbiomolbio.2007.03.006","article-title":"Gap junctional proteins of animals: the innexin\/pannexin superfamily","volume":"94","author":"MR Yen","year":"2007","journal-title":"Prog Biophys Mol Biol"},{"issue":"2","key":"pgen.1011944.ref062","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ydbio.2005.09.002","article-title":"Characterization of innexin gene expression and functional roles of gap-junctional communication in planarian regeneration","volume":"287","author":"T Nogi","year":"2005","journal-title":"Dev Biol"},{"issue":"9","key":"pgen.1011944.ref063","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.1440-169X.2006.00897.x","article-title":"Identification and origin of the germline stem cells as revealed by the expression of nanos-related gene in planarians","volume":"48","author":"K Sato","year":"2006","journal-title":"Dev Growth Differ"},{"issue":"14","key":"pgen.1011944.ref064","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1073\/pnas.0609708104","article-title":"nanos function is essential for development and regeneration of planarian germ cells","volume":"104","author":"Y Wang","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1011944.ref065","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1387\/ijdb.113452cg","article-title":"Decreased neoblast progeny and increased cell death during starvation-induced planarian degrowth","volume":"56","author":"C Gonz\u00e1lez-Est\u00e9vez","year":"2012","journal-title":"Int J Dev Biol"},{"key":"pgen.1011944.ref066","first-page":"25","article-title":"Sex-inducing substances terminate dormancy in planarian postembryonic reproductive development.","volume-title":"Advances in Invertebrate (Neuro)Endocrinology. A Collection of Reviews in the Post-Genomic Era Volume 1: Phyla Other Than Anthropoda","author":"K Sekii","year":"2020"},{"issue":"5","key":"pgen.1011944.ref067","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1002457","article-title":"GPCRs Direct Germline Development and Somatic Gonad Function in Planarians","volume":"14","author":"A Saberi","year":"2016","journal-title":"PLoS Biol"},{"key":"pgen.1011944.ref068","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mce.2010.06.018","article-title":"What are nuclear receptor ligands?","volume":"334","author":"FM Sladek","year":"2011","journal-title":"Mol Cell Endocrinol"},{"key":"pgen.1011944.ref069","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.58619","article-title":"Gap junctions deliver malonyl-CoA from soma to germline to support embryogenesis in Caenorhabditis elegans","volume":"9","author":"TA Starich","year":"2020","journal-title":"Elife"},{"issue":"2","key":"pgen.1011944.ref070","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3003045","article-title":"Gap junctions allow transfer of metabolites between germ cells and somatic cells to promote germ cell growth in the Drosophila ovary","volume":"23","author":"C Vachias","year":"2025","journal-title":"PLoS Biol"},{"key":"pgen.1011944.ref071","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.semcdb.2015.12.019","article-title":"Roles of connexins in testis development and spermatogenesis","volume":"50","author":"GM Kidder","year":"2016","journal-title":"Semin Cell Dev Biol"},{"issue":"11","key":"pgen.1011944.ref072","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.3390\/ijms22115918","article-title":"Pannexins and Connexins: Their Relevance for Oocyte Developmental Competence","volume":"22","author":"P Kordowitzki","year":"2021","journal-title":"Int J Mol Sci"},{"key":"pgen.1011944.ref073","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.semcdb.2019.09.002","article-title":"Gaps and barriers: Gap junctions as a channel of communication between the soma and the germline","volume":"97","author":"D Landschaft","year":"2020","journal-title":"Semin Cell Dev Biol"},{"issue":"1","key":"pgen.1011944.ref074","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ydbio.2011.08.014","article-title":"The gap junctional protein INX-14 functions in oocyte precursors to promote C. elegans sperm guidance","volume":"359","author":"JW Edmonds","year":"2011","journal-title":"Dev Biol"},{"issue":"12","key":"pgen.1011944.ref075","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.3390\/biom10121655","article-title":"A Limited and Diverse Set of Suppressor Mutations Restore Function to INX-8 Mutant Hemichannels in the Caenorhabditis elegans Somatic Gonad","volume":"10","author":"T Starich","year":"2020","journal-title":"Biomolecules"},{"issue":"3","key":"pgen.1011944.ref076","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1534\/genetics.114.168815","article-title":"Two classes of gap junction channels mediate soma-germline interactions essential for germline proliferation and gametogenesis in Caenorhabditis elegans","volume":"198","author":"TA Starich","year":"2014","journal-title":"Genetics"},{"key":"pgen.1011944.ref077","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.74955","article-title":"Innexin function dictates the spatial relationship between distal somatic cells in the Caenorhabditis elegans gonad without impacting the germline stem cell pool","volume":"11","author":"T Tolkin","year":"2022","journal-title":"Elife"},{"issue":"2","key":"pgen.1011944.ref078","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ydbio.2006.08.038","article-title":"The role of gap junctions in Caenorhabditis elegans oocyte maturation and fertilization","volume":"301","author":"SJ Whitten","year":"2007","journal-title":"Dev Biol"},{"issue":"24","key":"pgen.1011944.ref079","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1242\/dev.00804","article-title":"Mechanisms of germ cell specification across the metazoans: epigenesis and preformation","volume":"130","author":"CG Extavour","year":"2003","journal-title":"Development"},{"issue":"26","key":"pgen.1011944.ref080","doi-asserted-by":"crossref","first-page":"6625","DOI":"10.1242\/dev.00853","article-title":"Germ line stem cell differentiation in Drosophila requires gap junctions and proceeds via an intermediate state","volume":"130","author":"L Gilboa","year":"2003","journal-title":"Development"},{"issue":"10","key":"pgen.1011944.ref081","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1242\/dev.129.10.2529","article-title":"A germline-specific gap junction protein required for survival of differentiating early germ cells","volume":"129","author":"SI Tazuke","year":"2002","journal-title":"Development"},{"issue":"4","key":"pgen.1011944.ref082","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.semcdb.2006.05.004","article-title":"Two different evolutionary origins of stem cell systems and their molecular basis","volume":"17","author":"K Agata","year":"2006","journal-title":"Semin Cell Dev Biol"},{"issue":"24","key":"pgen.1011944.ref083","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1242\/dev.047969","article-title":"A conserved germline multipotency program","volume":"137","author":"CE Juliano","year":"2010","journal-title":"Development"},{"issue":"1","key":"pgen.1011944.ref084","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13227-022-00207-3","article-title":"Germline-related molecular phenotype in Metazoa: conservation and innovation highlighted by comparative transcriptomics","volume":"14","author":"G Piccinini","year":"2023","journal-title":"Evodevo"},{"issue":"1","key":"pgen.1011944.ref085","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/2041-9139-4-2","article-title":"Closing the circle of germline and stem cells: the Primordial Stem Cell hypothesis","volume":"4","author":"J Solana","year":"2013","journal-title":"Evodevo"},{"key":"pgen.1011944.ref086","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40851-018-0096-9","article-title":"A comprehensive comparison of sex-inducing activity in asexual worms of the planarian Dugesia ryukyuensis: the crucial sex-inducing substance appears to be present in yolk glands in Tricladida","volume":"4","author":"H Nakagawa","year":"2018","journal-title":"Zoological Lett"},{"issue":"10","key":"pgen.1011944.ref087","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1000509","article-title":"Genome-wide analyses reveal a role for peptide hormones in planarian germline development","volume":"8","author":"JJ Collins","year":"2010","journal-title":"PLoS Biol"},{"issue":"4","key":"pgen.1011944.ref088","doi-asserted-by":"crossref","first-page":"102625","DOI":"10.1016\/j.xpro.2023.102625","article-title":"Fractionation of a sex-inducing substance from flatworms using open-column chromatography and reverse-phase high-performance liquid chromatography","volume":"4","author":"K Sekii","year":"2023","journal-title":"STAR Protoc"},{"issue":"4","key":"pgen.1011944.ref089","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"B Langmead","year":"2012","journal-title":"Nat Methods"},{"issue":"1","key":"pgen.1011944.ref090","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.2251","article-title":"Streaming fragment assignment for real-time analysis of sequencing experiments","volume":"10","author":"A Roberts","year":"2013","journal-title":"Nat Methods"},{"issue":"10","key":"pgen.1011944.ref091","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"DJ McCarthy","year":"2012","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pgen.1011944.ref092","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"MD Robinson","year":"2010","journal-title":"Bioinformatics"},{"issue":"2","key":"pgen.1011944.ref093","doi-asserted-by":"crossref","DOI":"10.1002\/imt2.107","article-title":"Ultrafast one-pass FASTQ data preprocessing, quality control, and deduplication using fastp","volume":"2","author":"S Chen","year":"2023","journal-title":"Imeta"},{"issue":"17","key":"pgen.1011944.ref094","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"S Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"pgen.1011944.ref095","author":"H Li","year":"2013","journal-title":"Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv"},{"issue":"14","key":"pgen.1011944.ref096","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":"H Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"5","key":"pgen.1011944.ref097","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with Burrows-Wheeler transform","volume":"26","author":"H Li","year":"2010","journal-title":"Bioinformatics"},{"issue":"4","key":"pgen.1011944.ref098","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"R Patro","year":"2017","journal-title":"Nat Methods"},{"issue":"1","key":"pgen.1011944.ref099","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40851-021-00173-z","article-title":"D-Tryptophan enhances the reproductive organ-specific expression of the amino acid transporter homolog Dr-SLC38A9 involved in the sexual induction of planarian Dugesia ryukyuensis","volume":"7","author":"T Maezawa","year":"2021","journal-title":"Zoological Lett"},{"key":"pgen.1011944.ref100","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mod.2013.12.003","article-title":"Planarian D-amino acid oxidase is involved in ovarian development during sexual induction","volume":"132","author":"T Maezawa","year":"2014","journal-title":"Mech Dev"},{"issue":"4","key":"pgen.1011944.ref101","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2108\/zsj.29.265","article-title":"Existence of two sexual races in the planarian species switching between asexual and sexual reproduction","volume":"29","author":"K Kobayashi","year":"2012","journal-title":"Zoolog Sci"},{"key":"pgen.1011944.ref102","volume-title":"R: A language and environment for statistical computing","author":"Team RC R","year":"2021"},{"issue":"3","key":"pgen.1011944.ref103","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/jez.1401740303","article-title":"The cellular mechanism of the formation of a regeneration blastema of fresh-water planaria, Dugesia dorotocephala. I. The behavior of cells in a tiny body fragment isolated in vitro","volume":"174","author":"T Betchaku","year":"1970","journal-title":"J Exp Zool"},{"issue":"6","key":"pgen.1011944.ref104","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1046\/j.1440-169X.1997.t01-5-00008.x","article-title":"A planarian orthopedia homolog is specifically expressed in the branch region of both the mature and regenerating brain","volume":"39","author":"Y Umesono","year":"1997","journal-title":"Dev Growth Differ"},{"issue":"2","key":"pgen.1011944.ref105","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/dgd.12263","article-title":"Multi-color FISH facilitates analysis of cell-type diversification and developmental gene regulation in the Parasteatoda spider embryo","volume":"58","author":"Y Akiyama-Oda","year":"2016","journal-title":"Dev Growth Differ"},{"key":"pgen.1011944.ref106","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1749-8104-6-10","article-title":"Multicolor fluorescent in situ hybridization to define abutting and overlapping gene expression in the embryonic zebrafish brain","volume":"6","author":"G Lauter","year":"2011","journal-title":"Neural Dev"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1011944","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011944","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T18:49:43Z","timestamp":1764182983000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011944"}},"subtitle":[],"editor":[{"given":"Jean-Ren\u00e9","family":"Huynh","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,18]]},"references-count":106,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1011944","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,18]]}}}