{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:55:25Z","timestamp":1768524925723,"version":"3.49.0"},"posted":{"date-parts":[[2025,7,22]]},"group-title":"Developmental Biology","reference-count":112,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Neurodevelopment requires precise translational control, the disruption of which is implicated in various neurological disorders, including developmental delays, intellectual disability, and microcephaly. We report a novel role for the\n                  <jats:italic>Drosophila<\/jats:italic>\n                  CPEB-family protein Orb2, a translational regulator, in controlling brain size in a dose dependent manner. Loss of\n                  <jats:italic>orb2<\/jats:italic>\n                  results in larval brain hypotrophy, whereas\n                  <jats:italic>orb2<\/jats:italic>\n                  overexpression causes brain overgrowth. We demonstrate that\n                  <jats:italic>orb2<\/jats:italic>\n                  is required for neural stem cell development from embryonic stages through larval neurogenesis. Structure-function analysis reveals that Orb2 RNA-binding activity promotes brain growth, while its poly-Q and ZZ domains act to restrain overgrowth. Further genetic and biochemical evidence indicates that\n                  <jats:italic>orb2<\/jats:italic>\n                  functions upstream of the translational repressor Brain tumor (Brat), modulating Brat protein levels and, consequently, influencing brain size. These findings support a model wherein the antagonistic activities of Orb2 and Brat are critical for balanced brain growth during\n                  <jats:italic>Drosophila<\/jats:italic>\n                  neurodevelopment.\n                <\/jats:p>","DOI":"10.1101\/2025.07.18.665534","type":"posted-content","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T18:45:15Z","timestamp":1753209915000},"source":"Crossref","is-referenced-by-count":2,"title":["The CPEB ortholog Orb2 regulates brain size through the TRIM-NHL RNA-binding protein, Brain tumor"],"prefix":"10.64898","author":[{"given":"Taylor","family":"Hailstock","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Buehler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly 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