The genetic analysis of spermatogenesis in Drosophila melanogaster has led to the identification of several genes

The homeodomain is a DNA-binding motif present in a large number of eukaryotic transcription factors. To date, over 1,000 homeodomain proteins from over 100 different organisms have been described, making this family of DNA binding proteins one of the largest in biology (Banerjee-Basu et al., 1999; Banerjee-Basu et al., 2000; Gehring et al., 1994). Many homeodomain-containing factors, such as members of the Hox family, play critical roles in animal development (Cavodeassi et al., 2001; Hobert and Westphal, 2000; Lawrence and Morata, 1994; McGinnis and Krumlauf, 1992; Panganiban and Rubenstein, 2002; Trainor and Krumlauf, 2001). Perhaps in part because of their central role in animal development, many human diseases and genetic disorders are linked to mutations in homeodomain proteins (Abate-Shen, 2002; Buske and Humphries, 2000; Goodman and Scambler, 2001; Wallis and Muenke, 2000). Moreover, changes in the expression patterns, target genes and functions of homeodomain proteins are also thought to be a driving force in animal evolution (Mann and Carroll, 2002; Vervoort, 2002). Homeodomain proteins are classified into different groups depending upon the sequence of the homeodomain and immediately flanking amino acids, and the presence of other protein domains elsewhere in the protein (Gehring et al., 1994). One group of homeodomain proteins, called the TALE (for three amino acid loop extension) group, has an additional three amino acids separating the first and second alpha helices, resulting in a 63, instead of the more typical 60, amino acid homeodomain (Burglin, 1997). The TALE group is noteworthy for several reasons. Two TALE subgroups, MEIS and PBC, function as cofactors for the Hox homeodomain proteins (Mann and Affolter, 1998). At least for the regulation of some Hox target genes, a Hox/PBC/MEIS trimer is critical (Ferretti et al., 2000; Jacobs et al., 1999; Ryoo et al., 1999). In the PBC subgroup, the TALE-specific amino acids are Leu Ser Asn, which form part of a hydrophobic pocket that is directly contacted by the peptide Tyr-Pro-Trp-Met present in many Hox proteins (Passner et al., 1999; Piper et al., 1999). In addition to their role as Hox cofactors, the MEIS and PBC genes homothorax (hth) and extradenticle (exd) carry out several additional functions during Drosophila development. These genes are important for eye and antennal development and help to form the proximodistal axis in the thoracic appendages (Abu-Shaar and Mann, 1998; Bessa et al., 2002; Casares and Mann, 1998; Gonzalez-Crespo and Morata, 1996; Pai et al., 1998; Wu and Cohen, 1999). The Iroquois genes, which constitute a third TALE subgroup, are also important for patterning the appendages, as well as in neural and organ development (Cavodeassi et al., 2001). The TG interacting factors (TGIF) make up another interesting TALE subgroup. The founding member of this subgroup, TGIF, can be recruited to DNA directly, by binding to its target site, or indirectly, by virtue of its interaction with 2853 Development 130, 2853-2865 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00510