{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:36:44Z","timestamp":1770079004108,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,12]]},"group-title":"Developmental Biology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T00:00:00Z","timestamp":1715472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,10,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>C. elegans<\/jats:italic>\n                  molting offers a powerful entry point to understanding developmentally programmed apical extracellular matrix remodeling. However, the gene regulatory network controlling this process remains poorly understood. Focusing on targets of NHR-23, a key transcription factor that drives molting, we confirmed the Kunitz family protease inhibitor gene\n                  <jats:italic>mlt-11<\/jats:italic>\n                  as an NHR-23 target. Through reporter assays, we identified NHR-23-binding sites that are necessary and sufficient for epithelial expression. We generated a translational fusion and demonstrated that MLT-11 is localized to the cuticle and lined openings to the exterior (vulva, rectum, mouth). We created a set of strains expressing varied levels of MLT-11 by deleting endogenous\n                  <jats:italic>cis-<\/jats:italic>\n                  regulatory element sequences. Combined deletion of two\n                  <jats:italic>cis-<\/jats:italic>\n                  regulatory elements caused developmental delay, motility defects, and failure of the cuticle barrier. Inactivation of\n                  <jats:italic>mlt-11<\/jats:italic>\n                  by RNAi produced even more pronounced defects.\n                  <jats:italic>mlt-11<\/jats:italic>\n                  is necessary to pattern every layer of the adult cuticle, suggesting a broad patterning role prior to the formation of the mature cuticle. Together these studies provide an entry point into understanding how individual\n                  <jats:italic>cis-<\/jats:italic>\n                  regulatory elements function to coordinate expression of oscillating genes involved in molting and how MLT-11 ensures proper cuticle assembly.\n                <\/jats:p>","DOI":"10.1101\/2024.05.12.593762","type":"posted-content","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:55:10Z","timestamp":1715561710000},"source":"Crossref","is-referenced-by-count":1,"title":["The NHR-23-regulated putative protease inhibitor\n                  <i>mlt-11<\/i>\n                  gene is necessary for\n                  <i>C. elegans<\/i>\n                  cuticle structure and function"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6626-2615","authenticated-orcid":false,"given":"James Matthew","family":"Ragle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariela","family":"Turzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3130-6235","authenticated-orcid":false,"given":"An A.","family":"Vo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian T.","family":"Pham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-8936","authenticated-orcid":false,"given":"Jordan D.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024102113200813000_2024.05.12.593762v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43058-9"},{"key":"2024102113200813000_2024.05.12.593762v2.2","doi-asserted-by":"publisher","DOI":"10.2174\/1389203033487180"},{"key":"2024102113200813000_2024.05.12.593762v2.3","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyab006"},{"key":"2024102113200813000_2024.05.12.593762v2.4","doi-asserted-by":"crossref","unstructured":"Bada Juarez J , O\u2019Rourke D , Judge P , Liu L , Hodgkin J , Watts A . 2019. Lipodisqs for eukaryote lipidomics with retention of viability: Sensitivity and resistance to Leucobacter infection linked to C.elegans cuticle composition. 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