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.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Waase-Maurer, Carine"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Shai Shaham"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2007,"date_issued":"2007-01-01T08:00:00Z","date_published":"2007-01-01T08:00:00Z","updated_at":"2026-07-24T04:10:53Z","subjects":["cell death","C. elegans","ced-3 caspase","Life Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/10","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Shai Shaham"]},{"key":"dc:creator","label":"Author","values":["Waase-Maurer, Carine"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cell death","C. elegans","ced-3 caspase","Life Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/10"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Genetic and Molecular Characterization of Programmed Cell Death in the C.elegans Tail-Spike Cell"]}]}],"canonical_facts":{"dc:contributor":["Shai Shaham"],"dc:creator":["Waase-Maurer, Carine"],"dc:description.abstract":["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.
"],"dc:identifier":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/10"],"dc:subject":["cell death","C. elegans","ced-3 caspase","Life Sciences"],"dc:title":["Genetic and Molecular Characterization of Programmed Cell Death in the C.elegans Tail-Spike Cell"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:10:53Z"}