Genetic and Molecular Characterization of Programmed Cell Death in the C.elegans Tail-Spike Cell

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year

2007

Author dc:creator

• Waase-Maurer, Carine

Contributors dc:contributor

• Shai Shaham

• cell death
• C. elegans
• ced-3 caspase
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/10

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1009