Student Theses and Dissertations

Date of Award


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RU Laboratory

Shaham Laboratory


cell death, c.elegans, ced-3 caspase


Work in Caenorhabditis elegans has been instrumental in deciphering the molecular basis of programmed cell death. However, despite extensive characterization of broadacting cell death genes, the molecular events triggering cell-specific activation of the cell death machinery remain, for the most part, unknown. In some C. elegans somatic cells, transcription of the egl-1 /BH3-only gene is believed to promoted cell-specific death. EGL-1 protein inhibits the CED-9/Bcl-2 protein, resulting in release of the caspase activator CED-4/Apaf-1. Subsequent activation of CED-3 caspase by CED-4 leads to cell death. But despite the important role of egl-1 transcription in promoting CED-3 activity in cells destined to die, it remains unclear whether temporal control of cell death is mediated by egl-1 expression. Here, we establish the C. elegans tail-spike cell as an attractive model for studying the initiation of programmed cell death. We show that, while death of the tail-spike cell is dependent upon the ced-3 and ced-4 genes, egl-1 and ced-9 play only a minor role in the death of this cell, demonstrating that temporal control of cell death can be achieved in the absence of egl-1. We go on to show that the timing of tail-spike cell death onset is controlled by transcriptional induction of the ced-3 caspase. In the tailspike cell, ced-3 expression is induced minutes before the cell dies, and this induction is sufficient to promote the cell’s demise. Both ced-3 expression and cell death are dependent upon the transcription factor-encoding gene pal-1, the C. elegans homolog of the mammalian tumor suppressor gene Cdx2. PAL-1 can bind to ced-3 promoter sites critical for tail-spike cell death, suggesting that it promotes cell death by directly activating ced-3 transcription. Our results highlight a previously undescribed role for transcriptional regulation of caspases in controlling the timing of cell death onset during animal development.


A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

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