Cell-cell communication via Wnt signals represents a fundamental means by which animal development and homeostasis are controlled. The identification of components of the Wnt pathway is reaching saturation for the transduction process in receiving cells but is incomplete concerning the events occurring in Wnt-secreting cells. Here, we describe the discovery of a novel Wnt pathway component, Wntless (Wls/Evi), and show that it is required for Wingless-dependent patterning processes in Drosophila, for MOM-2-governed polarization of blastomeres in C. elegans, and for Wnt3a-mediated communication between cultured human cells. In each of these cases, Wls is acting in the Wnt-sending cells to promote the secretion of Wnt proteins. Since loss of Wls function has no effect on other signaling pathways yet appears to impede all the Wnt signals we analyzed, we propose that Wls represents an ancient partner for Wnts dedicated to promoting their secretion into the extracellular milieu.

Background: Transforming Growth Factor-β1 stimulated clone-22 (TSC-22) is assumed to act as a negative growth regulator and tumor suppressor. TSC-22 belongs to a family of putative transcription factors encoded by four distinct loci in mammals. Possible redundancy among the members of the TSC-22/Dip/Bun protein family complicates a genetic analysis. In Drosophila, all proteins homologous to the TSC-22/Dip/Bun family members are derived from a single locus called bunched (bun).

Nature has evolved an astonishing variety of genetic and epigenetic sex-determining systems which all achieve the same result, the generation of two sexes. Genetic and molecular analyses, mainly performed during the last 20 years, have gradually revealed the mechanisms that govern sexual differentiation in a few model organisms. In this review, we will introduce the sex-determining system of Drosophila and compare the fruitfly to the housefly Musca domestica and other Dipteran insects. Despite the ostensible variety, all these insects use the same basic strategy: a primary genetic signal that is different in males and females, a key gene that responds to the primary signal, and a double-switch gene that eventually selects between two alternative sexual programmes. These parallels, however, do not extend to the molecular level. Except for the double-switch gene doublesex at the end of the cascade, no functional homologies were found between more distantly related insects. In particular, Sex-lethal, the key gene that controls sexual differentiation in Drosophila, does not have a sex-determining function in any other genus studied so far. These results show that sex-determining cascades, in comparison to other regulatory pathways, evolve much more rapidly.

Gametogenesis in males and females differs in many ways. An important difference in Drosophila is that recombination between homologous chromosomes occurs only in female meiosis. Here, we report that this process relies on the correct functioning of Sex-lethal (Sxl) which is primarily known as the master gene in somatic sex determination. Certain alleles of this gene (Sxl(fs)) disrupt the germline, but not the somatic function of Sxl and cause an arrest of germ cell development during cystocyte proliferation. Using dominant suppressor mutations that relieve this early block in Sxl(fs) mutant females, we discovered additional requirements of Sxl for normal meiotic differentiation of the oocyte. Females mutant for Sxl(fs) and carrying a suppressor become fertile, but pairing of homologous chromosomes and formation of chiasmata is severely perturbed, resulting in an almost complete lack of recombinants and a high incidence of non-disjunction events. Similar results were obtained when germline expression of wild-type Sxl was compromised by mutations in virilizer (vir), a positive regulator of Sxl. Ectopic expression of a Sxl transgene in premeiotic stages of male germline development, on the other hand, is not sufficient to allow recombination to take place, which suggests that Sxl does not have a discriminatory role in this female-specific process. We propose that Sxl performs at least two tasks in oogenesis: an ‘early’ function in formation of the egg chamber, and a ‘late’ function in progression of the meiotic cell cycle, suggesting that both events are coordinated by a common mechanism.

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