Programmed cell death (PCD) is a common cell fate in metazoan development. PCD effectors are extensively studied, but how they are temporally regulated is less understood. Here we report a mechanism controlling tail-spike cell death onset during C. elegans development. We show that the Zn-finger transcription factor BLMP-1/Blimp1, which controls larval development timing, also regulates embryonic tail-spike cell death initiation. BLMP-1 functions upstream of CED-9/BCL-2 and in parallel to DRE-1/FBXO11, another CED-9 and tail-spike cell death regulator. BLMP-1 expression is detected in the tail-spike cell shortly after the cell is born, and blmp-1 mutations promote ced-9-dependent tail-spike cell survival. BLMP-1 binds ced-9/bcl-2 gene regulatory sequences, and inhibits ced-9 transcription just before cell-death onset. BLMP-1 and DRE-1 function together to regulate developmental timing, and their mammalian homologs regulate B-lymphocyte fate. Our results, therefore, identify roles for developmental timing genes in cell-death initiation, and suggest conservation of these functions.
BLMP-1 promotes developmental cell death in C. elegans by timely repression of ced-9/bcl-2 transcription
These authors contributed equally.
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Hang-Shiang Jiang, Piya Ghose, Hsiao-Fen Han, Yun-Zhe Wu, Ya-Yin Tsai, Huang-Chin Lin, Wei-Chin Tseng, Jui-Ching Wu, Shai Shaham, Yi-Chun Wu; BLMP-1 promotes developmental cell death in C. elegans by timely repression of ced-9/bcl-2 transcription. Development 2021; dev.193995. doi: https://doi.org/10.1242/dev.193995
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