Non-apoptotic death of the C. elegans linker cell is primed by MYRF-1 activation of pqn-41/polyQ

Yarychkivska, Olya, Liu, Simin, Horowitz, Lauren Bayer, Newland, Shiloh, Wu, Peipei, Mittal, Saiya, Tamura, Shogo, Novosolova, Tetiana, Ritter, David Faulkner, Lu, Yun, Ercan, Sevinç, Hammell, Christopher, Shaham, Shai (December 2025) Non-apoptotic death of the C. elegans linker cell is primed by MYRF-1 activation of pqn-41/polyQ. bioRxiv. ISSN 2692-8205 (Submitted)

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Abstract

Linker cell-type death (LCD) is a morphologically conserved non-apoptotic cell-death process with features resembling polyglutamine-dependent neurodegeneration. In C. elegans development, LCD eliminates the male-specific linker cell following its long-range migration. Using single-cell mRNA sequencing of migrating and dying linker cells, we identify myrf-1, encoding a membrane-bound transcription factor implicated in human developmental disorders, as a key LCD regulator. MYRF-1 translocates to the linker cell nucleus during early migration and, surprisingly, its auxin-inducible degradation then, but not later, blocks LCD. MYRF-1 directly binds known LCD genes, including pqn-41, encoding an aggregation-prone polyglutamine protein. Deleting a bona fide MYRF-1-binding site within pqn-41 promotes linker cell survival. Our findings reveal that linker cell death is primed well before cell demise takes place, temporally uncoupling death commitment and execution.

Item Type: Paper
Subjects: organism description > animal > C elegans
organism description > animal
CSHL Authors:
Communities: CSHL labs > Jackson lab
CSHL labs > Hammell C. lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 11 December 2025
Date Deposited: 05 Jan 2026 15:30
Last Modified: 05 Jan 2026 15:30
PMCID: PMC12712910
Related URLs:
URI: https://repository.cshl.edu/id/eprint/42053

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