{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:10:50Z","timestamp":1789157450200,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,7]]},"group-title":"Molecular Biology","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01AI167967"],"award-info":[{"award-number":["R01AI167967"]}]},{"award":["1275"],"award-info":[{"award-number":["1275"]}],"id":[{"id":"https:\/\/ror.org\/00np6vq88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1948-20240404"],"award-info":[{"award-number":["1948-20240404"]}],"id":[{"id":"https:\/\/ror.org\/00np6vq88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Lyda Hill Philanthropies"},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Plant-parasitic nematodes cause extensive crop losses that threaten global food security and create substantial economic hardship, yet strategies for their control remain limited. Although plant-parasitic nematodes have life cycles that mirror those of their free-living and animal-parasitic relatives, comparatively little is known about the signals that drive life-cycle progression. Dafachronic acids (DAs) are steroid hormones that control life cycle by activating DAF-12 nuclear receptors in\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  and animal-parasitic nematodes. To define whether an analogous pathway exists in plant-parasitic nematodes, we investigated the responsiveness of DAF-12 orthologs from six plant-parasitic nematode species to \u03947-DA, an endogenous DAF-12 ligand in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  and several animal-parasitic nematodes. We find that whereas some plant-parasitic nematode receptors are activated by \u03947-DA, others are not.\n                <\/jats:p>\n                <jats:p>\n                  Structural modeling of all six ligand-binding domains, together with docking of \u03947-DA into each model, indicates that responsiveness is governed by a combinatorial ligand-recognition network surrounding the ligand carboxylate rather than by any single contact residue. We further demonstrate that egg and second-stage juvenile extracts from the soybean cyst nematode,\n                  <jats:italic>Heterodera glycines<\/jats:italic>\n                  , lack detectable DA but contain distinct lipophilic fractions that activate its DAF-12 ortholog. Together, these findings suggest that many plant-parasitic nematodes utilize endogenous DAF-12 ligands that are structurally distinct from DA. Uncovering modulators of this pathway could lead to new strategies to combat nematode-driven crop loss.\n                <\/jats:p>","DOI":"10.64898\/2026.09.03.748874","type":"posted-content","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:30:14Z","timestamp":1788816614000},"source":"Crossref","is-referenced-by-count":0,"title":["Conservation of Nuclear Receptor DAF-12 with Evidence for Ligand Diversification in Plant-Parasitic Nematodes"],"prefix":"10.64898","author":[{"given":"Yanjie","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Wei","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Wendt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren G.","family":"Zacharias","sequence":"additional","affiliation":[{"name":"Children\u2019s Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey G.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Center for Human Nutrition, Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhai","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Yi","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Eric","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-641X","authenticated-orcid":false,"given":"Steven","family":"Kliewer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa 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