Developmental trajectories predict dendritic remodeling after injury.

Neurons in the adult central nervous system exhibit limited regenerative capacity, yet certain retinal ganglion cell subtypes exhibit greater resilience. We tested whether the timing of dendritic maturation shapes subtype-specific responses to injury. Reconstruction of over 1,000 retinal ganglion cells shows that ON-sustained (sONα) and ON-transient (tONα) cells follow distinct developmental trajectories: tONα cells reach peak dendritic size by postnatal day 10, while sONα cells mature by day 14. Post-injury, both subtypes undergo dendritic shrinkage; however, sONα cells remodel more rapidly and stabilize earlier. Computational modeling indicated that injury-induced morphologies resemble earlier developmental stages. Deletion of PTEN and SOCS3, which promotes axon regeneration, led to increased dendritic regression. These findings suggest that developmental timing constrains structural remodeling after injury and that axonal regeneration occurs at the expense of dendritic stability, highlighting a trade-off between axon growth and maintenance of dendritic architecture in adult retinal ganglion cells.