Abstract
In sex determination, globally acting genes control a spectrum of tissue-specific regulators to coordinate the overall development of an animal into one sex or the other. In mammals, primary sex determination initially occurs in the gonad, with the sex of other tissues specified as a secondary event. In insects and nematodes, globally acting regulatory pathways have been elucidated, but the more tissue- and organ-specific downstream effectors of these pathways remain largely unknown. We focus on the control of sexual dimorphism in the C. elegans gonad. We find that the forkhead transcription factor FKH-6 promotes male gonadal cell fates in XO animals. Loss-of-function fkh-6 mutant males have feminized gonads and often develop a vulva. In these mutant males, sex-specific cell divisions and migrations in the early gonad occur in the hermaphrodite mode, and hermaphrodite-specific gonadal markers are expressed. However, sexual transformation is not complete and the male gonad is malformed. By contrast, fkh-6 mutant hermaphrodites exhibit no sign of sex reversal. Most fkh-6 hermaphrodites form a two-armed symmetrical gonad resembling that of the wild type, but differentiation of the spermatheca and uterus is variably abnormal. The function of fkh-6 appears to be restricted to the gonad: fkh-6 mutants have no detectable defects in extra-gonadal tissues, and expression of a rescuing fkh-6 reporter is gonad-specific. Genetic and molecular analyses place fkh-6 downstream of tra-1, the terminal regulator of the global sex determination pathway, with respect to the first gonadal cell division. We conclude that fkh-6 regulates gonadogenesis in both sexes, but is male specific in establishing sexual dimorphism in the early gonad.
Highlights
Sex determination is the process by which cells, tissues and animals are directed to develop as one of two sexes
The gonad itself plays a dominant role: primary sex determination initially occurs in the gonad, which secretes hormones that induce appropriate sexual differentiation of other tissues
A forkhead transcription factor required for male gonadal morphogenesis
Summary
Sex determination is the process by which cells, tissues and animals are directed to develop as one of two sexes. The gonad must be specialized to support different modes of gametogenesis in each sex, and development of other tissues and organs is sexually dimorphic in most animals. The gonad itself plays a dominant role: primary sex determination initially occurs in the gonad, which secretes hormones that induce appropriate sexual differentiation of other tissues (reviewed by Nef and Parada, 2000). Cell-cell interactions play a role (Hunter and Wood, 1992), master regulators such as tra-1 of C. elegans or Sex lethal of Drosophila are expressed in all sexually dimorphic tissues, both gonadal and extra-gonadal, and cell-autonomously control their sexual differentiation (reviewed by Cline and Meyer, 1996). Despite differences in how sex determination is coordinated, some aspects of the process may be evolutionarily conserved between phyla: members of a protein family sharing the DM DNA-binding domain regulate sex determination in vertebrates, insects and nematodes (Erdman and Burtis, 1993; Lints and Emmons, 2002; Matsuda et al, 2002; Nanda et al, 2002; Raymond et al, 2000; Raymond et al, 1998)
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