While distinct programs are hypothesized to mediate degeneration of different parts of a cell, the precise cell biological and molecular events leading to compartment-specific destruction, such as neurite degeneration and pruning, are not well understood. We address this in the C. elegans tail-spike cell, a structurally complex cell that dies during embryonic development. This cell resembles a neuron, projecting an axon-like process towards the tail tip. Electron and fluorescence microscopy reveal that the tail-spike cell can be divided into three compartments: the cell body, the process proximal to the cell body, and a distal process segment. Scanning light-sheet microscopy indicates that the three compartments undergo region-specific degeneration with features resembling apoptotic death and clearance, axon fragmentation similar to that observed in Wallerian degeneration, and cytoplasmic transport and removal, respectively. We previously showed that cell body and process degeneration require CED-3/caspase and its adapter CED-4/Apaf-1, but are largely independent of EGL-1/BH3-only. Here we describe tail-spike cell compartment-specific killing and clearance programs. Importantly, we show that animals carrying a weak ced-3/caspase mutation can exhibit intact tail-spike cell soma or process alone, suggesting independent control of cell body and process degeneration by caspases. We also find that while ced-5/DOCK180 controls only cell body and not process engulfment, the conserved phagosome maturation gene sand-1 controls degradation of both, suggesting that independent engulfment programs converge on a common degradation machinery. We further report that the cell fusion receptor EFF-1, known to cell-autonomously mediate axon regeneration and dendrite sculpting, acts in surrounding cells to specifically promote degradation of the tail-spike cell distal process. Our studies uncover important roles for conserved genes in compartment-selective killing and degradation that are consistent with reports of differential requirements for process and cell body death and engulfment in other animals. We thus identify the tail-spike cell as an exciting and novel venue for understanding the cellular and molecular events governing complex cell elimination.
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