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Transcriptional upregulation of both egl-1 BH3-only and ced-3 caspase is required for the death of the male-specific CEM neurons.

Nehme R, Grote P, Tomasi T, Löser S, Holzkamp H, Schnabel R, Conradt B - Cell Death Differ. (2010)

Bottom Line: We found that in the CEMs, the transcriptional activation of both the egl-1 and ced-3 gene is necessary for apoptosis induction.Furthermore, we identified three genes, unc-86, lrs-1, and unc-132, which encode a POU homeodomain transcription factor, a leucyl-tRNA synthetase, and a novel protein with limited sequence similarity to the mammalian proto-oncoprotein and kinase PIM-1, respectively, that promote the expression of the ceh-30 gene in the CEMs. On the basis of these results, we propose that egl-1 and ced-3 transcription are coregulated in the CEMs to compensate for limiting proCED-3 levels, which most probably are a result of proCED-3 turn over.Finally, we present evidence that the timing of the death of the CEMs is controlled by TRA-1 Gli, the terminal global regulator of somatic sexual fate in C. elegans.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Dartmouth Medical School, Norris Cotton Cancer Center, Hanover, NH 3755, USA.

ABSTRACT
Most of the 131 cells that die during the development of a Caenorhabditis elegans hermaphrodite do so approximately 30 min after being generated. Furthermore, in these cells, the pro-caspase proCED-3 is inherited from progenitors and the transcriptional upregulation of the BH3-only gene egl-1 is thought to be sufficient for apoptosis induction. In contrast, the four CEM neurons, which die in hermaphrodites, but not males, die approximately 150 min after being generated. We found that in the CEMs, the transcriptional activation of both the egl-1 and ced-3 gene is necessary for apoptosis induction. In addition, we show that the Bar homeodomain transcription factor CEH-30 represses egl-1 and ced-3 transcription in the CEMs, thereby permitting their survival. Furthermore, we identified three genes, unc-86, lrs-1, and unc-132, which encode a POU homeodomain transcription factor, a leucyl-tRNA synthetase, and a novel protein with limited sequence similarity to the mammalian proto-oncoprotein and kinase PIM-1, respectively, that promote the expression of the ceh-30 gene in the CEMs. On the basis of these results, we propose that egl-1 and ced-3 transcription are coregulated in the CEMs to compensate for limiting proCED-3 levels, which most probably are a result of proCED-3 turn over. Similar coregulatory mechanisms for BH3-only proteins and pro-caspases may function in higher organisms to allow efficient apoptosis induction. Finally, we present evidence that the timing of the death of the CEMs is controlled by TRA-1 Gli, the terminal global regulator of somatic sexual fate in C. elegans.

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egl-1 is transcribed in surviving CEMs in masculinized unc-86(bc151), lrs-1(bc155), or unc-132(bc159) hermaphrodites(A) DIC and fluorescence images (Pegl-1his-24∷gfp) of CEMs (white arrows) or CEM corpses (white arrow heads) in wild-type hermaphrodites (+/+), sel-10(n1077), sel-10(n1077); ceh-30(bc272) or lrs-1(bc155); sel-10(n1077) hermaphrodites. (B) Summary of data obtained on Pegl-1his-24∷gfp expression. Green bars indicate the percentage of CEMs that were GFP-positive and blue bars indicate the percentage of CEMs that acquired a corpse-like morphology. All strains analyzed were homozygous for the integrated Pegl-1his-24∷gfp array bcIs37. The strain ceh-30(bc272);sel-10(n1077) was also homozygous for the integrated array bcIs9. The strains unc-86(bc151); sel-10(n1077) and lrs-1(bc155); sel-10(n1077) were homozygous for dpy-17(e164).
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Figure 3: egl-1 is transcribed in surviving CEMs in masculinized unc-86(bc151), lrs-1(bc155), or unc-132(bc159) hermaphrodites(A) DIC and fluorescence images (Pegl-1his-24∷gfp) of CEMs (white arrows) or CEM corpses (white arrow heads) in wild-type hermaphrodites (+/+), sel-10(n1077), sel-10(n1077); ceh-30(bc272) or lrs-1(bc155); sel-10(n1077) hermaphrodites. (B) Summary of data obtained on Pegl-1his-24∷gfp expression. Green bars indicate the percentage of CEMs that were GFP-positive and blue bars indicate the percentage of CEMs that acquired a corpse-like morphology. All strains analyzed were homozygous for the integrated Pegl-1his-24∷gfp array bcIs37. The strain ceh-30(bc272);sel-10(n1077) was also homozygous for the integrated array bcIs9. The strains unc-86(bc151); sel-10(n1077) and lrs-1(bc155); sel-10(n1077) were homozygous for dpy-17(e164).

Mentions: Using a transcriptional reporter (Pegl-1his-24∷gfp), we analyzed the expression of the egl-1 gene in the CEMs ~450 min after the first cell division (12, 16). We found that in wild-type hermaphrodites, the CEMs transcribe egl-1 and adopt a corpse-like morphology (Figure 3A, B, +/+). In contrast, in masculinized hermaphrodites, the CEMs do not transcribe egl-1 and do not adopt a corpse-like morphology (Figure 3A, B, sel-10(n1077)). As mentioned above, the loss of ceh-30 function causes the CEMs to inappropriately die in masculinized hermaphrodites. We found that the loss of ceh-30 function causes egl-1 to be inappropriately transcribed in the CEMs in masculinized hermaphrodites (Figure 2B, C, ceh-30(bc272); sel-10(n1077)). These results demonstrate that egl-1 transcriptional upregulation in the CEMs correlates with CEM death. In addition, they demonstrate that ceh-30 functions to repress egl-1 transcription in the CEMs in masculinized hermaphrodites (Figure 5).


Transcriptional upregulation of both egl-1 BH3-only and ced-3 caspase is required for the death of the male-specific CEM neurons.

Nehme R, Grote P, Tomasi T, Löser S, Holzkamp H, Schnabel R, Conradt B - Cell Death Differ. (2010)

egl-1 is transcribed in surviving CEMs in masculinized unc-86(bc151), lrs-1(bc155), or unc-132(bc159) hermaphrodites(A) DIC and fluorescence images (Pegl-1his-24∷gfp) of CEMs (white arrows) or CEM corpses (white arrow heads) in wild-type hermaphrodites (+/+), sel-10(n1077), sel-10(n1077); ceh-30(bc272) or lrs-1(bc155); sel-10(n1077) hermaphrodites. (B) Summary of data obtained on Pegl-1his-24∷gfp expression. Green bars indicate the percentage of CEMs that were GFP-positive and blue bars indicate the percentage of CEMs that acquired a corpse-like morphology. All strains analyzed were homozygous for the integrated Pegl-1his-24∷gfp array bcIs37. The strain ceh-30(bc272);sel-10(n1077) was also homozygous for the integrated array bcIs9. The strains unc-86(bc151); sel-10(n1077) and lrs-1(bc155); sel-10(n1077) were homozygous for dpy-17(e164).
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Figure 3: egl-1 is transcribed in surviving CEMs in masculinized unc-86(bc151), lrs-1(bc155), or unc-132(bc159) hermaphrodites(A) DIC and fluorescence images (Pegl-1his-24∷gfp) of CEMs (white arrows) or CEM corpses (white arrow heads) in wild-type hermaphrodites (+/+), sel-10(n1077), sel-10(n1077); ceh-30(bc272) or lrs-1(bc155); sel-10(n1077) hermaphrodites. (B) Summary of data obtained on Pegl-1his-24∷gfp expression. Green bars indicate the percentage of CEMs that were GFP-positive and blue bars indicate the percentage of CEMs that acquired a corpse-like morphology. All strains analyzed were homozygous for the integrated Pegl-1his-24∷gfp array bcIs37. The strain ceh-30(bc272);sel-10(n1077) was also homozygous for the integrated array bcIs9. The strains unc-86(bc151); sel-10(n1077) and lrs-1(bc155); sel-10(n1077) were homozygous for dpy-17(e164).
Mentions: Using a transcriptional reporter (Pegl-1his-24∷gfp), we analyzed the expression of the egl-1 gene in the CEMs ~450 min after the first cell division (12, 16). We found that in wild-type hermaphrodites, the CEMs transcribe egl-1 and adopt a corpse-like morphology (Figure 3A, B, +/+). In contrast, in masculinized hermaphrodites, the CEMs do not transcribe egl-1 and do not adopt a corpse-like morphology (Figure 3A, B, sel-10(n1077)). As mentioned above, the loss of ceh-30 function causes the CEMs to inappropriately die in masculinized hermaphrodites. We found that the loss of ceh-30 function causes egl-1 to be inappropriately transcribed in the CEMs in masculinized hermaphrodites (Figure 2B, C, ceh-30(bc272); sel-10(n1077)). These results demonstrate that egl-1 transcriptional upregulation in the CEMs correlates with CEM death. In addition, they demonstrate that ceh-30 functions to repress egl-1 transcription in the CEMs in masculinized hermaphrodites (Figure 5).

Bottom Line: We found that in the CEMs, the transcriptional activation of both the egl-1 and ced-3 gene is necessary for apoptosis induction.Furthermore, we identified three genes, unc-86, lrs-1, and unc-132, which encode a POU homeodomain transcription factor, a leucyl-tRNA synthetase, and a novel protein with limited sequence similarity to the mammalian proto-oncoprotein and kinase PIM-1, respectively, that promote the expression of the ceh-30 gene in the CEMs. On the basis of these results, we propose that egl-1 and ced-3 transcription are coregulated in the CEMs to compensate for limiting proCED-3 levels, which most probably are a result of proCED-3 turn over.Finally, we present evidence that the timing of the death of the CEMs is controlled by TRA-1 Gli, the terminal global regulator of somatic sexual fate in C. elegans.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Dartmouth Medical School, Norris Cotton Cancer Center, Hanover, NH 3755, USA.

ABSTRACT
Most of the 131 cells that die during the development of a Caenorhabditis elegans hermaphrodite do so approximately 30 min after being generated. Furthermore, in these cells, the pro-caspase proCED-3 is inherited from progenitors and the transcriptional upregulation of the BH3-only gene egl-1 is thought to be sufficient for apoptosis induction. In contrast, the four CEM neurons, which die in hermaphrodites, but not males, die approximately 150 min after being generated. We found that in the CEMs, the transcriptional activation of both the egl-1 and ced-3 gene is necessary for apoptosis induction. In addition, we show that the Bar homeodomain transcription factor CEH-30 represses egl-1 and ced-3 transcription in the CEMs, thereby permitting their survival. Furthermore, we identified three genes, unc-86, lrs-1, and unc-132, which encode a POU homeodomain transcription factor, a leucyl-tRNA synthetase, and a novel protein with limited sequence similarity to the mammalian proto-oncoprotein and kinase PIM-1, respectively, that promote the expression of the ceh-30 gene in the CEMs. On the basis of these results, we propose that egl-1 and ced-3 transcription are coregulated in the CEMs to compensate for limiting proCED-3 levels, which most probably are a result of proCED-3 turn over. Similar coregulatory mechanisms for BH3-only proteins and pro-caspases may function in higher organisms to allow efficient apoptosis induction. Finally, we present evidence that the timing of the death of the CEMs is controlled by TRA-1 Gli, the terminal global regulator of somatic sexual fate in C. elegans.

Show MeSH
Related in: MedlinePlus