The Drosophila apterous (ap) gene encodes a protein of the LIM-homeodomain family. Many transcription factors of this class have been conserved during evolution; however, the functional significance of their structural conservation is generally not known. ap is best known for its fundamental role as a dorsal selector gene required for patterning and growth of the wing, but it also has other important functions required for neuronal fasciculation, fertility, and normal viability. We isolated mouse (mLhx2) and human (hLhx2) ap orthologs, and we used transgenic animals and rescue assays to investigate the conservation of the Ap protein during evolution. We found that the human protein LHX2 is able to regulate correctly ap target genes in the fly, causes the same phenotypes as Ap when ectopically produced, and most importantly rescues ap mutant phenotypes as efficiently as the fly protein. In addition, we found striking similarities in the expression patterns of the Drosophila and murine genes. Both mLhx2 and ap are expressed in the respective nerve cords, eyes, olfactory organs, brain, and limbs. These results demonstrate the conservation of Ap protein function across phyla and argue that aspects of its expression pattern have also been conserved from a common ancestor of insects and vertebrates.As DNA sequence data generated by the genome projects fill the databases, an increasing number of genes related by sequence are being identified in the human and model systems genomes. These sequence comparisons are expected to provide invaluable insight into the function of human genes (for example see ref.

The LIM homeodomain (LIM-HD) protein Apterous (Ap) and its cofactor DLDB/CHIP control dorso- ventral (D/V) patterning and growth of Drosophila wing. To investigate the molecular mechanisms of Ap/CHIP function we altered their relative levels of expression and generated mutants in the LIM1, LIM2 and HD domains of Ap, as well as in the LIM-interacting and self-association domains of CHIP. Using in vitro and in vivo assays we found that: (i) the levels of CHIP relative to Ap control D/V patterning; (ii) the LIM1 and LIM2 domains differ in their contributions to Ap function; (iii) Ap HD mutations cause weak dominant negative effects; (iv) overexpression of ChipDeltaSAD mutants mimics Ap lack-of-function, and this dominant negative phenotype is caused by titration of Ap because it can be rescued by adding extra Ap; and (v) overexpression of ChipDeltaLID mutants also causes an Ap lack-of-function phenotype, but it cannot be rescued by extra Ap. These results support the model that the Ap-CHIP active complex in vivo is a tetramer.

Here we describe and compare the expression patterns of the murine genes Lhx2 and Msx1 and their Drosophila orthologues apterous (ap) and muscle-segment homeobox (msh). We find that Lhx2 and Msx1 show complementary patterns of expression in most tissues including the neural and cranial epithelium, pituitary gland, olfactory organs, and neural tube; in contrast, Lhx2 and Msx1 are coexpressed in the developing limbs. Strikingly, the spatial relationship between ap and msh expression in Drosophila is very reminiscent of the expression of their murine orthologues. ap and msh show complementary expression in the leg and antennal imaginal discs, brain and ventral ganglion of the central nervous system (CNS), but both are coexpressed in the wing imaginal disc. These observations suggest conservation in the regulation of these genes between Drosophila and mice.

To evaluate basic informativeness of commercially available microsatellite markers in the Taiwanese population, 190 unrelated Taiwanese children were genotyped using ABI PRISM Linkage Mapping Set-HD5. The average heterozygosity in Taiwanese was slightly lower than that in Caucasians among these 811 microsatellite markers. There were 50 marker loci with heterozygosities lower than 50%. Moreover, allelic distributions at many of the loci were significantly different in two ethnic groups. The results reported here represent a valuable database for disease genes mapping in the Taiwanese population. This database can be easily accessed at the Web site of Vita Genomics, Inc.