The C. elegans protein CEH-30 protects male-specific neurons from apoptosis independently of the Bcl-2 homolog CED-9.
The developmental control of apoptosis is fundamental and important. We report that the Caenorhabditis elegans Bar homeodomain transcription factor CEH-30 is required for the sexually dimorphic survival of the male-specific CEM (cephalic male) sensory neurons; the homologous cells of hermaphrodites undergo programmed cell death. We propose that the cell-type-specific anti-apoptotic gene ceh-30 is transcriptionally repressed by the TRA-1 transcription factor, the terminal regulator of sexual identity in C. elegans, to cause hermaphrodite-specific CEM death. The established mechanism for the regulation of specific programmed cell deaths in C. elegans is the transcriptional control of the BH3-only gene egl-1, which inhibits the Bcl-2 homolog ced-9; similarly, most regulation of vertebrate apoptosis involves the Bcl-2 superfamily. In contrast, ceh-30 acts within the CEM neurons to promote their survival independently of both egl-1 and ced-9. Mammalian ceh-30 homologs can substitute for ceh-30 in C. elegans. Mice lacking the ceh-30 homolog Barhl1 show a progressive loss of sensory neurons and increased sensory-neuron cell death. Based on these observations, we suggest that the function of Bar homeodomain proteins as cell-type-specific inhibitors of apoptosis is evolutionarily conserved.
Howard Hughes Medical Institute and MIT Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Hillel T
HT
Schwartz
H Robert
HR
Horvitz
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D018509:DNA, Helminth / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D017238:Genes, Helminth; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009475:Neurons, Afferent / Q000166:cytology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012727:Sex Characteristics; D019849:Sex Determination Processes; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D018509:DNA, Helminth; C112486:EGL-1 protein, C elegans; D018398:Homeodomain Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D014157:Transcription Factors