The endoplasmic reticulum promotes microtubule organization and region-specific disassembly to execute Compartmentalized Cell Elimination.

Specialized cells, such as neurons, die during development and disease. How subcellular organization and interactions across diverse compartments direct death is not well-understood. We examine this by studying the Compartmentalized Cell Elimination (CCE) developmental death program of the C. elegans tail-scaffolding cell (TSC). We find endoplasmic reticulum (ER) shape genes and the microtubule (MT) severase SPAS-1/Spastin, all linked to neurodegeneration, cooperate to promote CCE. Super-resolution imaging reveals profound spatiotemporal dynamics of MTs and the ER across CCE, including enrichment in a stereotyped degenerative node. We observe an ER-dependent non-centrosomal microtubule organizing center (ncMTOC) in the degenerative node, where the ER locally promotes both MT organization and SPAS-1/Spastin-mediated MT severing. The ER is spatially confined, such that SPAS-1/Spastin also has an ER-independent role. Our study expands our understanding of the cell biology of specialized cell death during development and presents molecular links to pathological neurodegeneration, paving the way to neurodegenerative therapies.