The Questions of Developmental Biology

The sex-lethal gene as the pivot for sex determination
Interpreting the x:a ratio
The first phase of Drosophila sex determination involves reading the X:A ratio. What
elements on the X chromosome are "counted," and how is this information used? It appears that
high values of the X:A ratio are responsible for activating the feminizing switch gene Sex-lethal
(Sxl). In XY cells, Sxl remains inactive during the early stages of development (Cline 1983; Salz
et al. 1987). In XX Drosophila,Sxl is activated during the first 2 hours after fertilization, and this
gene transcribes a particular embryonic type of Sxl mRNA that is found for only about 2 hours
more (Salz et al. 1989). Once activated, the Sxl gene remains active because its protein product is
able to bind to and activate its own promoter (Sánchez and Nöthiger 1983).
This female-specific activation of Sxl is thought to be stimulated by "numerator
proteins" encoded by the X chromosome. These constitute the X part of the X:A ratio.
Cline (1988) has demonstrated that these numerator proteins include Sisterless-a and Sisterless-b.
These proteins bind to the "early" promoter of the Sxl gene to promote its transcription shortly
after fertilization.
The "denominator proteins" are autosomally encoded proteins such as Deadpan and
Extramacrochaetae. These proteins block the binding or activity of the numerator proteins (Van
Doren et al. 1991; Younger-Shepherd et al. 1992). The denominator proteins may actually be able
to form inactive heterodimers with the numerator proteins (Figure 17.17). It appears, then, that
the X:A ratio is measured by competition between X-encoded activators and autosomally
encoded repressors of the promoter of the Sxl gene.