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Our goal is to understand how linear information encoded in genomic DNA functions to control cell fates during development. The Drosophila genome is about one twentieth the size of the human genome. However, despite its smaller size, most developmental genes and at least half of the disease- and cancer-causing genes in man are conserved in Drosophila, making Drosophila a particularly important model system for the study of human development and disease. One of the important groups of conserved developmental genes are the homeotic genes. In Drosophila, the homeotic genes specify cell identities at both the embryonic and adult stages. The genes encode homeodomain-containing transcription factors that control cell fates by regulating the transcription of downstream target genes. The homeotic genes are expressed in precise spatial patterns that are crucial for the proper determination of cell fate. Both loss of expression and ectopic expression in the wrong tissues lead to changes in cell fate. The changes provide powerful assays for identifying the trans-acting factors that regulate the homeotic genes and the cis-acting sequences through which they act. The trans-acting factors are also conserved between Drosophila and human and have important functions, not only in development but also in stem-cell maintenance and cancer.

Genetic defects that cause male infertility are also common in both man and Drosophila. Mutations to male sterility in Drosophila are about 15% as common as mutations to lethality, suggesting that a substantial proportion of the Drosophila genome may be required only for male fertility. As expected from these genetic data, as much as 20-25% of the Drosophila proteome may be expressed only in males. The proportions of genes required for male fertility do not differ significantly between the X chromosome and the autosomes, however, translocations that exchange large portions of the X chromosome and one of the two large autosomes frequently disrupt spermatogenesis and cause male sterility, both in Drosophila and in mammals.  This male sterility is not caused by disruption of individual genes, but by interference with differential regulation of sex chromosomes and autosomes during spermatogenesis.

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