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Comments on Milne CA et al. (1995) International C. elegans Meeting "A CANDIDATE PRIMARY SEX DETERMINATION LOCUS ON THE X CHROMOSOME, fox-1" (0)
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Milne CA, Skipper M, & Hodgkin JA (1995). A CANDIDATE PRIMARY SEX DETERMINATION LOCUS ON THE X CHROMOSOME, fox-1 presented in International C. elegans Meeting. Unpublished information; cite only with author permission.
Sex in C. elegans is determined by the ratio of X chromosomes to autosomes (X:A ratio), such that 2X:2A animals are hermaphrodite and 1X:2A animals are male. This primary signal is required to set the state of both sex determination and dosage compensation. It is not known how the X:A ratio is assessed, or how many sites contribute to the numerator (X) and denominator (A) components of this ratio. A dose-sensitive region near the left end of the X chromosome was identified by X chromosome duplications and subsequently by testing individual cosmids from this region. Increasing the copy number of certain of these cosmids has feminizing and lethal effects on XO animals. The lethality arises from improper dosage compensation. These cosmids define fox-1 (Feminizing locus On the X), which appears to act as a major numerator site (Hodgkin et al., Development 120: 3681, 1994). A 1.7 kb embryonic cDNA from this region was found to encode a protein containing an RNA-binding motif. Further investigation of this transcript indicates that it is trans- spliced to an SL1 leader sequence. Developmental northern blot analysis indicates that two related transcripts are detectable at early stages, one at 1.8 kb (corresponding to the cDNA) and a less abundant species at 2.4 kb. In mid-larval stages these transcripts are not detectable, and in adults only the 1.8 kb transcript is seen. Direct tests of the role of these transcripts in generating the Fox-1 phenotype are in progress, as well as genetic and molecular experiments directed at disrupting fox-1, in order to explore what other functions it may have.