{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:29Z","timestamp":1792790369333,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,25]]},"group-title":"Developmental Biology","reference-count":76,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Dental and Craniofacial Research","award":["DE023017"],"award-info":[{"award-number":["DE023017"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Dental and Craniofacial Research","award":["DE030971"],"award-info":[{"award-number":["DE030971"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"crossref"}]},{"name":"School of Dental Medicine, University of Colorado Anschutz","id":[{"id":"https:\/\/ror.org\/03wmf1y16","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Pathogenic variants in\n                  <jats:italic>POLR1C<\/jats:italic>\n                  , which encodes a shared subunit of RNA Polymerases (Pols) I and III, cause Treacher Collins syndrome (TCS) and POLR3-related leukodystrophy. While Pol I and Tp53-dependent mechanisms have been implicated in the pathogenesis of TCS, the basis of hypomyelination in\n                  <jats:italic>POLR1C<\/jats:italic>\n                  -associated POLR3-related leukodystrophy remains incompletely understood. Here, we show that\n                  <jats:italic>polr1c<\/jats:italic>\n                  mutant zebrafish exhibit reduced myelination in addition to previously described craniofacial anomalies. Oligodendrocyte precursor cells exhibit increased activation of the Tp53 pathway; however, these cells do not undergo apoptosis. Consistent with this finding,\n                  <jats:italic>tp53<\/jats:italic>\n                  inhibition reduces cell death in\n                  <jats:italic>polr1c<\/jats:italic>\n                  mutants but fails to restore myelination, indicating that myelination deficits are not driven by Tp53-dependent progenitor loss in this model.\n                  <jats:italic>polr1c<\/jats:italic>\n                  mutants also exhibit reduced rRNA transcription by Pol I and reduced expression of some Pol III-transcribed tRNAs. Altogether, these data indicate distinct tissue-specific responses to\n                  <jats:italic>polr1c<\/jats:italic>\n                  deficiency and suggest persistent impairment of rRNA transcription contributes to deficient myelin development. These findings expand the developmental consequences of\n                  <jats:italic>polr1c<\/jats:italic>\n                  loss and advance our understanding of the molecular basis of\n                  <jats:italic>POLR1C<\/jats:italic>\n                  -associated diseases.\n                <\/jats:p>","DOI":"10.64898\/2026.09.24.752997","type":"posted-content","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:10:13Z","timestamp":1790338213000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of\n                  <i>polr1c<\/i>\n                  disrupts myelination in a zebrafish model of\n                  <i>POLR1C<\/i>\n                  -associated disease"],"prefix":"10.64898","author":[{"given":"Lauren B.","family":"Sands","sequence":"first","affiliation":[{"name":"Department of Craniofacial, Oral and Materials Sciences, University of Colorado Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille E.A.","family":"Goo","sequence":"additional","affiliation":[{"name":"Department of Craniofacial, Oral and Materials Sciences, University of Colorado Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura K.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Genetics, University of Colorado Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey T.","family":"Lubash","sequence":"additional","affiliation":[{"name":"Department of Craniofacial, Oral and Materials Sciences, University of Colorado Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6819-1419","authenticated-orcid":false,"given":"M. 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