Yan Lab
25th International Worm Meeting, University of California, Davis,
June 28 to July 2, 2025
Abstract: Regulation of Local Translation of Flippases by OMA-1/ZFP36L is Required for Axon Degeneration
Axon degeneration is a hallmark of neurodegenerative diseases and aging, with NMNAT and Sarm1 identified as key regulators of axon degeneration. However, the exact underlying mechanisms remain incompletely understood. C. elegans has been widely used as a model organism in neurobiology. However, the prevailing belief that C. elegans lacked Wallerian degeneration or employed different mechanisms to regulate axon degeneration compared to Drosophila and mice. Here, we challenge this notion by demonstrating that the neurons of adult C. elegans do undergo Wallerian degeneration, but with a slower speed. In this study, we show that severed axons exhibit progressive degeneration over days, mirroring morphological features observed in other species. Furthermore, we provide genetic evidence that C. elegans employs the conserved NMNAT-Sarm1 pathway to drive axon degeneration, establishing it as a suitable model for studying this process. Using C. elegans as the model organism, we identify C. elegans OMA-1 and its mammalian homologs, ZFP36L1 and ZFP36L2, as novel mediators of axon degeneration acting downstream of Sarm1. OMA-1/ZFP36L regulates the mRNA decay of the conserved flippase TAT-2/ATP8B2, suppressing its local translation. The absence of TAT-2 in injured axons promotes degeneration, highlighting the critical role of local mRNA regulation in axon integrity. Our findings not only indicate C. elegans as a powerful model organism for studying axon degeneration but also uncover a conserved new mechanism governing axon degeneration.