Genomics at the CGB :: Projects
Sex Genes in Drosophila
Project Leader:
Justen Andrews
In Drosophila sex is determined by the number of X-chromosomes relative to the number of
autosomes -- embryos with two X-chromosomes develop as females and those with one
X-chromosome develop as males. The most dramatic sexual dimorphism is found in the
germline. Germ cells differentiate to make either eggs or sperm with radically
different cellular specializations. This is reflected at the molecular level with germ
cells showing dramatic sex-biased gene expression. How is this regulated? From previous
studies we know that appropriate sexual differentiation of germ cells into female
gametes requires: (i) a cell autonomous signal from the number of X chromosomes, (ii) a
non-cell autonomous signal from the surrounding soma, and (iii) the function of several
genes in the "germline sex-determination pathway", So far these genes include: ovo,
otu, stil, snf, and Sxl. We are seeking to unravel this regulatory network in the
following ways:
1. Molecular structure and function of key regulatory genes. To date, we
have focused on molecular studies of ovo. These studies have revealed that it encodes
both an activator and a repressor transcription factor isoforms that bind to specific
sites in the ovo and otu promoters and directly regulates their transcription. We will
be undertaking similar functional studies on new genes believed to participate in the
germline sex-determination pathway (see point 3 below).
2. Genome-wide germline gene regulation. We have used EST sequencing and
microarrays to investigate genome-wide sex-biased gene expression in the germline. We
are currently working to refine expression profiling techniques to identify genes that
are co-regulated in specific cells at specific stages of oogeneisis. This work is
facilitated by the Drosophila Genomics Resource Center (DGRC) of which I am a
co-Director. Please see the DGRC web site at: http://dgrc.cgb.indiana.edu/.
3. Identifying new players. Our most recent work is implicating novel genes
in this regulatory pathway. Using microarrays we have identified genes showing altered
expression in response to altered ovo transcription factor activity. We are following up
on 22 genes that show the most dramatic responses. These genes are either direct or
indirect targets of OVO. We are combining this analysis with the bioinformatic,
identification of clustered OVO binding site motifs, and data mining various sources of
functional information.
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