How an organism determines which of two alternative pathways of sexual differentiation to follow is a fundamental problem in development. In C. elegans, a free-living soil nematode, the ratio of X chromosomes to sets of autosomes determines whether the organism develops into a self-fertilizing hermaphrodite (2A:2X) or a male (2A:1X). In addition, a set of autosomal genes responsive to the chromosome balance has been identified as essential for either hermaphrodite development or male development. 1. One of our aims is to determine how C. elegans assesses the ratio of X chromosomes to autosomes and how this measurement affects the expression of sex-determining genes and dosage-compensating genes downstream in the pathway. One approach is a genetical one, isolating male and hermaphrodite lethal mutations and suppressors of genes known to be involved in dosage compensation. A second approach is to perform a descriptive analysis at the cellular level, of intersexual animals, induced either by mutation or by altering X dosage. This description will provide a broader framework in which to think about the consequences of altering the correct assessment of the X:A ratio. Because sexual differentiation is determined by the chromosomal composition, it is often necessary to impose a further mechanism to insure that expression of genes on sex chromosomes is kept equal in the different sexes. 2. another aim is to gain an understanding of the mechanism of dosage compensation. Our approach is to analyze genetically and biochemically loci known to affect the expression of X-linked genes and to identify new loci involved in this process. The biochemical analysis involves assaying X-linked gene expression in animals with mutations suspected to alter dosage compensation in order to determine if, in fact, they do. In addition, the analysis involves the molecular cloning of loci involved in dosage compensation.
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