{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:39:12Z","timestamp":1785404352073,"version":"3.56.0"},"posted":{"date-parts":[[2025,5,13]]},"group-title":"Molecular Biology","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["1R01GM154212-01"],"award-info":[{"award-number":["1R01GM154212-01"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21HD089476"],"award-info":[{"award-number":["R21HD089476"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The complexity of cellular functions necessitates intricate pathways that govern protein synthesis, transport, and degradation; yet the mechanisms governing the trafficking of key developmental proteins\n                  <jats:italic>in vivo<\/jats:italic>\n                  remain incompletely understood. N-Myc downstream-regulated genes (NDRGs) have recently emerged as stress-responsive proteins with roles in protein trafficking, but their functions during normal embryogenesis are largely unknown. Here, we identify N-Myc downstream-regulated gene 1b (Ndrg1b) as a novel regulator of N-cadherin (N-cad,\n                  <jats:italic>cdh2<\/jats:italic>\n                  ) trafficking during zebrafish muscle development. We show that\n                  <jats:italic>ndrg1b<\/jats:italic>\n                  is broadly expressed during embryonic and larval stages and is required for proper skeletal muscle morphogenesis. Loss of Ndrg1b disrupts N-cad localization and impairs cell adhesion\n                  <jats:italic>in vitro<\/jats:italic>\n                  , highlighting a key role in maintaining tissue integrity. Mechanistically, Ndrg1b promotes the recycling of N-cad to the plasma membrane, identifying it as a novel component of the endocytic trafficking machinery\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Given N-cad\u2019s central role in development and disease, these findings provide new insight into how its localization is fine-tuned during morphogenesis. This work also expands the functional repertoire of NDRGs beyond stress response, suggesting that Ndrg1b \u2013 and potentially other NDRG family members \u2013 may broadly regulate transmembrane protein trafficking in a context-dependent manner. Furthermore, these findings may shed greater light on the etiology of Charcot-Marie-Tooth Disease type 4D, which has been linked to mutations in NDRG1.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>GRAPHICAL ABSTRACT<\/jats:title>\n                  <jats:p>(generated in Biorender)<\/jats:p>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"652902v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key takeaways<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        Zebrafish\n                        <jats:italic>ndrg1b<\/jats:italic>\n                        is ubiquitously expressed in early development\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Loss of Ndrg1b is strikingly similar to the loss of N-cadherin<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Ndrg1b is required for the proper subcellular localization of N-cadherin in muscle cells and for the proper morphogenesis of this organ<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Loss of Ndrg1b reduces the ability of cells to aggregate\n                        <jats:italic>in vitro<\/jats:italic>\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                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