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This variability may be linked to differences in developmental programs that overlap with the genetic pathways that mediate regeneration. To explore this correlation, we compared the structural changes in mouse retinal ganglion cells during development with those occurring after axonal injury. The dendritic trees of over 1,000 ganglion cells were reconstructed at different developmental stages, revealing that each cell type follows a distinct timeline. ON-sustained (sON\u03b1) cells reach maturity by P14, whereas ON-transient (tON\u03b1) cells achieve their maximum dendritic size by P10. Modeling of the dendritic changes indicate that while sON\u03b1 and tON\u03b1 follow similar growth programs the onset of growth was later in sON\u03b1. After optic nerve crush, the remodeling of dendritic architecture differed between the two cell-types. sON\u03b1 cells exhibited rapid dendritic shrinkage, while tON\u03b1 cells shrank more gradually with changes in branching features. Following injury, sON\u03b1 cells reverted to an earlier developmental state than tON\u03b1 cells. In addition, after co-deletion of PTEN and SOC3, neurons appeared to regress further back in developmental time. Our results provide evidence that a ganglion cell\u2019s resilience to injury and regenerative potential is predicted by its maturation timeline. Understanding these intrinsic differences could inform targeted neuroprotective interventions.<\/jats:p>","DOI":"10.1101\/2025.02.28.640775","type":"posted-content","created":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T05:30:21Z","timestamp":1740807021000},"source":"Crossref","is-referenced-by-count":2,"title":["Predicting the Regenerative Potential of Retinal Ganglion Cells Based on Developmental Growth Trajectories"],"prefix":"10.64898","author":[{"given":"Joana RF","family":"Santos","sequence":"first","affiliation":[{"name":"VIB \u2013 Neuro-Electronics Research Flanders, Leuven, Belgium"},{"name":"KU Leuven, Department of Biology & Leuven Brain Institute, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"VIB \u2013 Neuro-Electronics Research Flanders, Leuven, Belgium"},{"name":"KU Leuven, Department of Biology & Leuven Brain Institute, Leuven, Belgium"},{"name":"Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien","family":"Andries","sequence":"additional","affiliation":[{"name":"KU Leuven, Department of Biology & Leuven Brain Institute, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Masin","sequence":"additional","affiliation":[{"name":"KU Leuven, Department of Biology & Leuven Brain Institute, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bram","family":"Nuttin","sequence":"additional","affiliation":[{"name":"VIB \u2013 Neuro-Electronics Research Flanders, Leuven, Belgium"},{"name":"KU Leuven, Department of Biology & Leuven Brain Institute, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Reinhard","sequence":"additional","affiliation":[{"name":"VIB \u2013 Neuro-Electronics Research Flanders, Leuven, Belgium"},{"name":"SISSA, Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieve","family":"Moons","sequence":"additional","affiliation":[{"name":"KU Leuven, Department of Biology & Leuven Brain Institute, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Cuntz","sequence":"additional","affiliation":[{"name":"Frankfurt Institute for Advanced Studies, 60438 Frankfurt am Main, Germany"},{"name":"Ernst Str\u00fcngmann Institute (ESI) for Neuroscience in cooperation with the Max Planck Society, 60528 Frankfurt am Main, Germany"},{"name":"ICAR3R \u2013 Interdisciplinary Centre for 3Rs in Animal Research, Justus Liebig University Gie\u00dfen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Farrow","sequence":"additional","affiliation":[{"name":"VIB \u2013 Neuro-Electronics Research Flanders, Leuven, Belgium"},{"name":"KU Leuven, Department of Biology & Leuven Brain Institute, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041111481956000_2025.02.28.640775v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2011.01.014"},{"key":"2026041111481956000_2025.02.28.640775v1.2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1131-22.2022"},{"key":"2026041111481956000_2025.02.28.640775v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.04.012"},{"key":"2026041111481956000_2025.02.28.640775v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(97)00041-5"},{"key":"2026041111481956000_2025.02.28.640775v1.5","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1447"},{"key":"2026041111481956000_2025.02.28.640775v1.6","unstructured":"Tran NM , Shekhar K , Whitney IE , Jacobi A , Benhar I , Hong G , et al. 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