Epidermal and ECM Damage Following Pinch Injury Restricts Dendrite Regeneration in

Neuronal dendrites can be injured by a number of insults, but the cellular mechanism by which dendrites respond to tissue injury and undergo repair is poorly understood. Much of the field's progress has evaluated dendrite regeneration following laser injury. While precise, laser injury does not accurately model the real-world damage to surrounding tissue that would accompany neuronal injury. Here, we modify a pinch injury technique to injure both the dendrites and their surrounding tissues in Significance Statement: Neuronal dendrites are injured in clinical conditions, such as stroke, traumatic brain injury, and neonatal hypoxia. Dendrites also degenerate in the early stages of a number of neurodegenerative diseases. The role of surrounding tissues in dendrite regeneration is poorly characterized, especially considering that neuronal injury is typically accompanied by broad tissue damage. Our data evaluates dendrite regeneration following an injury that better mirrors real-world conditions and demonstrates that broad tissue damage diminishes a neuron's capacity to regenerate its dendrites. Our findings show that neurons preferentially regrow into intact, undamaged tissue environments, addressing a large gap in the field's knowledge: how damage to the surrounding tissue limits neuron regeneration after injury. Visual Abstract: