Regulation of LIM homeodomain activity in vivo: a tetramer of dLDB and apterous confers activity and capacity for regulation by dLMO.

Dorsal-ventral axis formation in the Drosophila wing depends on the activity of the LIM homeodomain transcription factor Apterous and its cofactor, dLDB/Chip. We present evidence that Apterous activity depends on the formation of a LIM homeodomain dimer bridged by a dimer of cofactor. We show that Apterous activity levels are regulated in vivo by dLMO, an antagonist of homodimer formation. Making use of a constitutively active form of Apterous and dominant-negative forms of Apterous and dLDB/Chip, we show that the normal function of dLMO is to downregulate Apterous activity and that the dLMO mutant phenotype is due to excess Apterous activity. These findings may point to a general mechanism for regulation of LIM homeodomain protein activity.