Chip-mediated partnerships of the homeodomain proteins Bar and Aristaless with the LIM-HOM proteins Apterous and Lim1 regulate distal leg development.

Proximodistal patterning in Drosophila requires division of the developing leg into increasingly smaller, discrete domains of gene function. The LIM-HOM transcription factors apterous (ap) and Lim1 (also known as dlim1), and the homeobox genes Bar and aristaless (al) are part of the gene battery required for the development of specific leg segments. Our genetic results show that there are posttranslational interactions between Ap, Bar and the LIM-domain binding protein Chip in tarsus four, and between Al, Lim1 and Chip in the pretarsus, and that these interactions depend on the presence of balanced amounts of such proteins. We also observe in vitro protein binding between Bar and Chip, Bar and Ap, Lim1 and Chip, and Al and Chip. Together with the previous evidence for interactions between Ap and Chip, these results suggest that these transcription factors form protein complexes during leg development. We propose that the different developmental outcomes of LIM-HOM function are due to the precise identity and dosage of the interacting partners present in a given cell.