Sexual dimorphism in the nervous system of C. elegans is a result of differential numbers of cell divisions, different cell fates, or programmed cell death (PCD). The cephalic companion neurons (CEMs), four sensory neurons thought to be involved in mating behaviour, and the hermaphrodite specific neurons (HSNs), two motoneurons necessary for egg laying, are sexually dimorphic as a result of PCD (Sulston and Horvitz, 1977). The HSNs and CEMs are born in embryos of both sexes but are subsequently eliminated by PCD in males (HSNs) or hermaphrodites (CEMs). The death of the CEMs and the survival of the HSNs in hermaphrodites are regulated by the most downstream factor of the sex-determination pathway, the zinc-finger transcription factor TRA-1 ( tra , transformer), and by the key activator of the cell-death pathway, the BH3-only protein EGL-1( egl , egg-laying defective). Because TRA-1 functions to repress the
egl-1 gene in the HSNs but to activate
egl-1 in the CEMs, cell-specific factors must exist that act with TRA-1 to regulate PCD in these sexually dimorphic neurons. Gain-of-function (gf) mutations of the gene
egl-41 cause the CEMs to inappropriately survive in hermaphrodites. In order to identify genes required for CEM survival, we performed a screen for mutations that cause the CEMs to be absent in
egl-41 (gf) hermaphrodites and identified three mutations,
bc151 ,
bc155 and
bc159 . All three mutations cause the CEMs to be absent in
egl-41 (gf) hermaphrodites and also in otherwise wild-type males.
bc151 ,
bc155 and
bc159 affect the formation and/or specification of the CEMs rather than their sex specific death, since the absence of the CEMs can not be suppressed by a
ced-3 (lf) mutation.
bc151 represents an allele of
unc-86 , which codes for a POU homeodomain transcription factor previously shown to control neuronal specification in many neurons, including the HSNs and CEMs (Desai et al., 1988; Finney et al., 1988).
bc155 causes 88% of the CEMs in
egl-41 (gf) hermaphrodites to be absent. We are in the process of mapping this mutation using SNP mapping.
bc159 causes 100% of the CEMs in
egl-41 (gf) hermaphrodites to be absent. Moreover,
bc159 animals are Egl and slightly Unc. The observation that the sisters of the dorsal CEMs, the dorsal URA neurons, are present in
bc159 animals indicates that the last cell division, which gives rise to the dorsal URAs and the dorsal CEMs, takes place, but that the CEMs fail to differentiate. The reduced expression of the differentiation marker P
glr-4 glr-4 ::gfp in the URAs furthermore indicates that
bc159 affects the fate of additional neurons. Epistasis analysis with
cfi-1 (CEM fate inhibitor), a gene that represses the expression of CEM-specific genes in some neurons including the URAs (Shaham and Bargmann, 2002), revealed that the gene defined by
bc159 acts downstream of or in parallel to
cfi-1 . The identification of this gene and further characterization of the
bc159 phenotype will reveal new insights into the specification of the CEMs and other neurons. Using transformation rescue experiments, we have obtained cosmid rescue of the
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unc-86 encodes a protein with a homeodomain and extended similarity to transcription factors. Cell 55, 757-69. Shaham, S. and Bargmann, C. I. (2002). Control of neuronal subtype identity by the C. elegans ARID protein CFI-1. Genes Dev 16, 972-83. Sulston, J. E. and Horvitz, H. R. (1977). Post-embryonic cell lineages of the nematode, Caenorhabditis elegans . Dev Biol 56, 110-56.