{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T05:46:48Z","timestamp":1775972808436,"version":"3.50.1"},"posted":{"date-parts":[[2025,5,17]]},"group-title":"Neuroscience","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T00:00:00Z","timestamp":1747440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institutes of Health Office of the Director","award":["R21OD033664"],"award-info":[{"award-number":["R21OD033664"]}]},{"name":"National Institutes of Health Office of the Director","award":["S10OD032136"],"award-info":[{"award-number":["S10OD032136"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Rebuilding functional neuronal circuits after injury in the adult central nervous system (CNS) is unachievable for many vertebrates. In pro-regenerative models, it is unclear how regeneration and re-wiring is achieved in the CNS over long distances. The size and opacity of the adult vertebrate brain makes it difficult to study re-innervation patterns and dynamic cellular interactions during long-distance axon regeneration. Here, we harnessed the properties of the small and transparent adult\n                  <jats:italic>Danionella cerebrum<\/jats:italic>\n                  for longitudinal\n                  <jats:italic>in vivo<\/jats:italic>\n                  imaging of retinal ganglion cell axon regeneration, correlating cellular events with functional recovery. Our results suggest that, following optic nerve injury, the arborization pattern of re-innervation differs after regeneration, suggesting that new axon tracts are formed to restore functional vision. Additionally, myelin is not restored to pre-injury levels, even after functional recovery is achieved. The\n                  <jats:italic>D. cerebrum<\/jats:italic>\n                  model provides a unique opportunity to visualize and experimentally manipulate the spatial and temporal events during CNS regeneration in intact adult vertebrates.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Research highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Reveals the neuro-regenerative potential of the small, transparent adult vertebrate<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>Danionella cerebrum<\/jats:italic>\n                        , a novel model for central nervous system (CNS) repair studies.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Demonstrates CNS regeneration using two visual functional recovery assays and longitudinal\n                        <jats:italic>in vivo<\/jats:italic>\n                        imaging of a novel adult axonogenesis reporter transgenic line, a myelin reporter line, and mosaic labeling of retinal ganglion cell axons.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Establishes a method to compare retinal ganglion cell axons before and after CNS injury in adult\n                        <jats:italic>D. cerebrum<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Positions\n                        <jats:italic>D. cerebrum<\/jats:italic>\n                        as a powerful platform for visualizing long-distance CNS regeneration in intact adult vertebrates.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Graphical abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>\n                      Longitudinal live imaging of adult\n                      <jats:italic>D. cerebrum<\/jats:italic>\n                      reveals the formation of a new axon and myelin pattern post optic nerve injury along with functional recovery.\n                    <\/jats:bold>\n                  <\/jats:p>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"653880v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                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