EOR-1/PLZF promotes WAH-1/AIF-dependent compartment-specific corpse clearance

Programmed cell death (PCD) is a crucial, evolutionarily conserved process required for development and homeostasis. We previously described a genetically non-canonical apoptotic, highly ordered cell death program called Compartmentalized Cell Elimination (CCE) in the C. elegans morphologically complex tail-spike epithelial cell (TSC). Here, we define a role for the transcription factor EOR-1/PLZF as an important, compartment-specific, regulator of CCE. We identify EOR-1 specifically in the dying cell's own clearance, which can function downstream of CED-3/caspase, which is essential for TSC killing. Whereas prior studies implicate EOR-1 in programmed cell killing, we provide mechanistic detail in a new developmental cell elimination context. Specifically, we find EOR-1/PLZF positively regulates Apoptosis Inducing Factor homolog WAH-1 during CCE. We identify WAH-1 as a new contributor to two steps of soma-specific clearance during CCE, acting in the dying cell: corpse recognition-internalization, and phagosome maturation-corpse resolution following engulfment. In the absence of EOR-1/PLZF as well as WAH-1/AIF, the TSC soma remains uninternalized, persisting with exaggerated nuclei previously undescribed. We suggest a role of the scramblase SCRM-1 in TSC soma internalization by the phagocyte and show spatiotemporal specificity of the presentation of the canonical apoptotic corpse recognition signal phosphatidylserine (PS) on the TSC. We also report that in the absence of CPS-6/Endonuclease G, the internalized TSC soma corpse arrests at the phagolysosomal stage, also yielding exaggerated nuclei. This suggests that WAH-1 also promotes DNA degradation during CCE during phagosome maturation. Our work provides new molecular and cell biological insights into CCE and expands our understanding of the transcriptional regulation of corpse clearance.