Axon Regeneration Requires a Conserved MAP Kinase Pathway

TLDR

Neuronal regeneration can restore function, yet many neurons fail to regenerate because intrinsic pathways are not activated. The study aims to determine whether activating the DLK‑1 MAP kinase pathway can promote axon regeneration, potentially guiding therapeutic strategies. Using Caenorhabditis elegans motor neurons, the authors demonstrate that the DLK‑1 MAP kinase pathway is essential for axon regeneration. Loss of the DLK‑1 MAP kinase pathway abolishes regeneration, while its activation enhances regeneration and promotes growth‑cone migration, indicating the cascade is required to transition mature neurons from an aplastic to a growth‑competent state.

Abstract

Regeneration of injured neurons can restore function, but most neurons regenerate poorly or not at all. The failure to regenerate in some cases is due to a lack of activation of cell-intrinsic regeneration pathways. These pathways might be targeted for the development of therapies that can restore neuron function after injury or disease. Here, we show that the DLK-1 mitogen-activated protein (MAP) kinase pathway is essential for regeneration in Caenorhabditis elegans motor neurons. Loss of this pathway eliminates regeneration, whereas activating it improves regeneration. Further, these proteins also regulate the later step of growth cone migration. We conclude that after axon injury, activation of this MAP kinase cascade is required to switch the mature neuron from an aplastic state to a state capable of growth.