{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:58:43Z","timestamp":1791568723645,"version":"4.3.4"},"reference-count":111,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP240100491"],"award-info":[{"award-number":["DP240100491"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    In vertebrate embryos, M\u00fcllerian ducts give rise to the female reproductive tract. Here, we present a comprehensive analysis of M\u00fcllerian duct differentiation using single cell transcriptomics in the chicken embryo, a unique model for duct development. The data reveal greater cellular complexity of M\u00fcllerian duct differentiation than previously understood. Transcriptomic profiling of early formed M\u00fcllerian ducts identifies molecular signatures for the M\u00fcllerian duct Epithelium (MDE) and the M\u00fcllerian Duct Mesenchyme (MDM), the two principle compartments of the M\u00fcllerian duct. The MDE expresses\n                    <jats:italic>PAX2, LHX1, WNT7, LGR5, PDGFA\/D<\/jats:italic>\n                    , and\n                    <jats:italic>CDH1\/2<\/jats:italic>\n                    . The MDM is marked by\n                    <jats:italic>WNT4, EMX2, POSTN, OSR1, VIM,DMRT<\/jats:italic>\n                    and the EMT markers\n                    <jats:italic>ZEB1\/2<\/jats:italic>\n                    . In the male, the regressing mesenchyme (MDM) has a unique molecular signature, expressing the transcription factors\n                    <jats:italic>MSX1, MSX2, RUNX2, GATA5, DLX3<\/jats:italic>\n                    and\n                    <jats:italic>DLX5<\/jats:italic>\n                    , and the signaling regulators\n                    <jats:italic>DKK4<\/jats:italic>\n                    and\n                    <jats:italic>NRG1<\/jats:italic>\n                    (Neuregulin). Single cell transcript profiling of the regressing male mesenchyme identifies new genes implicated in duct regression, including the WNT antagonist, DKK4. DKK4, responds to Anti-Mullerian Hormone induction and can induce duct regression when ectopically expressed in females. The duct mesenchyme in the female follows a different fate, with a molecular signature comprising\n                    <jats:italic>SMARCA2\/ HMGA2\/ZEB1\/2\/TWIST1\/2\/DMRT2<\/jats:italic>\n                    and persistent expression of\n                    <jats:italic>FOXE1, OSR2<\/jats:italic>\n                    and\n                    <jats:italic>HGF<\/jats:italic>\n                    (Hepatocyte Growth Factor). Cell clusters in the developing female ducts reflects spatial pre-patterning of the duct prior to later regionalisation. In contrast to AMH-mediated bilateral M\u00fcllerian duct regression in males, female chicken embryos show an unusual pattern of left duct differentiation and contralateral right duct regression. We find that right female duct does not regress in the same manner as in males, being transcriptionally distinct and lacking a population of regressing mesenchyme, despite presumably being mediated by AMH, as in males.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012302","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:44:06Z","timestamp":1791567846000},"page":"e1012302","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["New insights into M\u00fcllerian duct differentiation provided by single cell transcriptomics in the chicken embryo"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2541-2841","authenticated-orcid":true,"given":"Juan Lan","family":"Tan","sequence":"first","affiliation":[{"name":"Monash University","place":["Clayton, Australia"],"department":["Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Barugahare","sequence":"additional","affiliation":[{"name":"Monash University","place":["Clayton, Australia"],"department":["Monash Genomics and Bioinformatics Platform"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-6652","authenticated-orcid":true,"given":"Andrew Thomas","family":"Major","sequence":"additional","affiliation":[{"name":"The University of Melbourne","place":["Melbourne, Australia"],"department":["School of Bioscience, Faculty of Science"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1670-5545","authenticated-orcid":true,"given":"Craig Allen","family":"Smith","sequence":"additional","affiliation":[{"name":"Monash University","place":["Clayton, Australia"],"department":["Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"pgen.1012302.ref001","volume-title":"Reproductive physiology of vertebrates","author":"A van Tienhoven","year":"1983"},{"key":"pgen.1012302.ref002","first-page":"3","article-title":"Sex determination and differentiation","volume-title":"Raven Press","author":"FW George","year":"1994"},{"key":"pgen.1012302.ref003","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev.ph.40.030178.001431","article-title":"Sexual differentiation","volume":"40","author":"JD Wilson","year":"1978","journal-title":"Annu Rev Physiol"},{"issue":"2","key":"pgen.1012302.ref004","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/mrd.1080360231","article-title":"Role of the oviduct in the development of the mouse embryo","volume":"36","author":"N Minami","year":"1993","journal-title":"Mol Reprod 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