C. elegans has two natural sexes, XO males and XX hermaphrodites. The hermaphrodites are simply self-fertile females whose only male character is the ability to make the limited number of sperm used solely for internal self-fertilization. This modified female is therefore able to reproduce in the absence of any other individual. However, given the opportunity, she will mate with a male, use his sperm preferentially, and produce more progeny as a consequence. Males can be produced from rare, spontaneous X chromosome nondisjunction events during hermaphrodite reproduction or as 50% of the outcross progeny in a mating between a male and a hermaphrodite.

Sex is determined by an X chromosome counting mechanism in which the dose of X chromosomes is measured relative to the ploidy, the number of sets of autosomes (Nigon 1951; Madl and Herman 1979). Worms with an X:A ratio of 1.0 are hermaphrodites, and those with an X:A ratio of 0.5 are males. Animals can discriminate between even smaller differences in the signal: Those with an X:A ratio of 0.67 (2X:3A) are males, whereas those with an X:A ratio of 0.75 (3X:4A) are hermaphrodites. Although the organism uses an “X:A mechanism” of sex determination, wild-type animals are diploid and therefore normally only count X chromosomes.

The degree of overt sexual dimorphism in C. elegans is extensive, with 30% of the 959 somatic nuclei in the adult hermaphrodite and 40% of the 1031 somatic nuclei in the adult male being sexually specialized. In fact, sexual dimorphism occurs in all tissue types and arises in almost all major branches of the cell lineage (Sulston and Horvitz 1977; Kimble and Hirsh 1979; Kimble and Sharrock 1983; Sulston et al. 1983; Hodgkin 1988). Although some adult structures such as the pharynx and the main body musculature appear to be identical between the sexes, other aspects of the anatomy and many aspects of behavior are dramatically different (Fig. 1). For example, the hermaphrodite has a two-armed gonad in which spermatogenesis (160 sperm produced per arm) occurs during the last larval stage, followed by oogenesis during adulthood. In each arm, the sperm are stored internally in a specialized compartment, and the oocytes are fertilized as they pass through the compartment into the uterus. The embryos are laid through the vulva, an opening in the ventral hypodermis that also serves as the site of entry for male-produced sperm. The hermaphrodite tail is relatively unspecialized and tapers to a thin point. In contrast, the male is both shorter (∼30%) and thinner than the hermaphrodite and is highly specialized for mating (see also Emmons and Sternberg, this volume). For example, the male tail is equipped with various specialized sensory and copulatory structures that enable him to locate the vulva and successfully inseminate the hermaphrodite. The male also differs in that it has a single-armed gonad, which produces approximately 3000 sperm. The hypodermal cells that divide and give rise to the vulva in hermaphrodites fail to divide in the male and instead join the hypodermal syncytium. Extensive dimorphism also occurs in both the musculature and the nervous system. Sex-specific muscles and neurons are involved in egg-laying behavior in hermaphrodites as well as mating behavior, copulation, and locomotory behavior in males. The intestine is functionally specialized for yolk production only in hermaphrodites (Kimble and Sharrock 1983).

Figure 1

Sexual dimorphism in adult males and hermaphrodites.

Embryonic development is almost identical between the sexes. The first visible sign of sexual dimorphism appears two thirds of the way through embryogenesis with the programmed cell deaths of two hermaphrodite-specific motor neurons in the male and four male-specific sensory neurons in the hermaphrodite (Sulston et al. 1983). Other sexual dimorphisms arise during embryogenesis and the first three larval stages, but the differences in males and hermaphrodites become most prominent in the L4 larval stage and in the adult (Sulston and Horvitz 1977). Diverse strategies are used to generate sexual dimorphism, including sex-specific programmed cell death, generation of sex-specific blast cells, alternative lineages adopted by a common primordium, and differential gene expression in tissues with identical cell lineages.

The first aspect of sexual dimorphism to develop in worms is one shared by all somatic cells: a difference in the average rate of X-linked gene expression, a consequence of dosage compensation. The process of dosage compensation equalizes the amount of X-linked gene products between the sexes despite a twofold difference in X chromosome dose (Wood et al. 1985; Meyer and Casson 1986; DeLong et al. 1987; Meneely and Wood 1987). The onset of dosage compensation occurs at approximately the 30-cell stage (Chuang et al. 1994). Dosage compensation is achieved by modulating the transcript levels of active X-linked genes, rather than by inactivating an X chromosome. In particular, hermaphrodites reduce transcript levels from both X chromosomes by half (Meyer and Casson 1986; Chuang et al. 1994). This hermaphrodite-specific process is essential for the viability of XX animals (Hodgkin 1983; Meyer and Casson 1986; Nusbaum and Meyer 1989; Plenefisch et al. 1989) and is lethal if implemented in males (Miller et al. 1988).

Achieving proper differentiation of the two sexes requires the coordination of a large number of developmental events that are spatially, mechanistically, and temporally distinct. All of the numerous aspects of sexual dimorphism, stemming from the earliest regulation of zygotic gene expression soon after fertilization to some of the latest events during gametogenesis in the mature adult, are controlled and coordinated by a regulatory gene hierarchy. This hierarchy includes genes that comprise the X:A signal itself, genes that respond directly to the signal to control coordinately both sex determination and dosage compensation, and more specialized genes that regulate either sex determination or dosage compensation.