biostudies-literatureUnknown110(10)Watkins TAThe cell intrinsic factors that determine whether a neuron regenerates or undergoes apoptosis in response to axonal injury are not well defined. Here we show that the mixed-lineage dual leucine zipper kinase (DLK) is an essential upstream mediator of both of these divergent outcomes in the same cell type. Optic nerve crush injury leads to rapid elevation of DLK protein, first in the axons of retinal ganglion cells (RGCs) and then in their cell bodies. DLK is required for the majority of gene expression changes in RGCs initiated by injury, including induction of both proapoptotic and regeneration-associated genes. Deletion of DLK in retina results in robust and sustained protection of RGCs from degeneration after optic nerve injury. Despite this improved survival, the number of axons that rProceedings of the National Academy of Sciences of the United States of America4039-44https://www.ebi.ac.uk/biostudies/studies/S-EPMC3593899biostudies-literatureDLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury.PMC3593899Huntwork-Rodriguez SJiang ZYang JWang BTessier-Lavigne MWatkins TAKaminker JSLewcock JWModrusan ZEastham-Anderson JfalseDLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury.The cell intrinsic factors that determine whether a neuron regenerates or undergoes apoptosis in response to axonal injury are not well defined. Here we show that the mixed-lineage dual leucine zipper kinase (DLK) is an essential upstream mediator of both of these divergent outcomes in the same cell type. Optic nerve crush injury leads to rapid elevation of DLK protein, first in the axons of retinal ganglion cells (RGCs) and then in their cell bodies. DLK is required for the majority of gene expression changes in RGCs initiated by injury, including induction of both proapoptotic and regeneration-associated genes. Deletion of DLK in retina results in robust and sustained protection of RGCs from degeneration after optic nerve injury. Despite this improved survival, the number of axons that r2013-01-01T00:00:00Z2013 Mar2025-04-19T09:06:19.328Z2019-03-27T01:05:52ZS-EPMC35938992343116410.1073/pnas.1211074110