{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T07:02:06Z","timestamp":1775890926563,"version":"3.50.1"},"posted":{"date-parts":[[2025,1,30]]},"group-title":"Developmental Biology","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Nucleoredoxin (\n                  <jats:italic>Nxn<\/jats:italic>\n                  ) encodes a multi-functional enzyme with oxidoreductase activity that regulates many different signaling pathways and cellular processes in a redox-dependent manner. Rare\n                  <jats:italic>NXN<\/jats:italic>\n                  mutations are reported in individuals with recessive Robinow syndrome, which involves mesomelic skeletal dysplasia, short stature, craniofacial dysmorphisms, and incompletely penetrant heart and palate defects. Here we report that\n                  <jats:italic>Nxn<\/jats:italic>\n                  is expressed in the ventral diencephalon and developing pituitary gland, and that\n                  <jats:italic>Nxn<\/jats:italic>\n                  deficient mice have pituitary dysmorphology and craniofacial abnormalities that include defects in the skull base and cleft palate.\n                  <jats:italic>Nxn<\/jats:italic>\n                  mutant mice exhibit reduced WNT signaling and reduced differentiation of pituitary stem cells into hormone-producing cells. These results suggest patients with Robinow syndrome could benefit from evaluation by endocrinologists for pituitary structural imaging and hormone insufficiency.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"simple\">\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>Nxn<\/jats:italic>\n                        deficiency causes neonatal lethality, cleft palate, craniofacial abnormalities, and other structural birth defects.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>Nxn<\/jats:italic>\n                        deficiency causes pituitary dysmorphology.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Analysis of scRNA seq reveals delayed trajectory during early pituitary cell differentiation.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>Nxn<\/jats:italic>\n                        deficiency reduces canonical and non-canonical Wnt signaling in developing pituitary glands.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>Nxn<\/jats:italic>\n                        deficiency reduces stem cell differentiation into pituitary hormone-producing cells.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.01.30.635771","type":"posted-content","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T02:35:11Z","timestamp":1738290911000},"source":"Crossref","is-referenced-by-count":1,"title":["Nucleoredoxin regulates WNT signaling during pituitary stem cell differentiation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9505-4682","authenticated-orcid":false,"given":"Michelle L.","family":"Brinkmeier","sequence":"first","affiliation":[{"name":"Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109-5618, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0912-9594","authenticated-orcid":false,"given":"Leonard Y. M.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109-5618, USA"},{"name":"Current address: Department of Physiology and Biophysics, Renaissance School of Medicine, State University of New York, Stonybrook, NY 11794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1161-5337","authenticated-orcid":false,"given":"Sean P.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of South Carolina, Columbia, SC, 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7650-8722","authenticated-orcid":false,"given":"Diana K.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of South Carolina, Columbia, SC, 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eve C.","family":"Rhoads","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109-5618, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8556-3379","authenticated-orcid":false,"given":"Sally A.","family":"Camper","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109-5618, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7354-5691","authenticated-orcid":false,"given":"Shannon W.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of South Carolina, Columbia, SC, 29208, 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