Conservation of the expression and function of apterous orthologs in Drosophila and mammals

Abstract

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.

Delineation of Multiple Subpallial Progenitor Domains by the Combinatorial Expression of Transcriptional Codes

“…Images were obtained using a cooled CCD camera (DC500; Leica, Nussloch, Germany). The following cDNA probes were used in this study: Dbx1 (Lu et al, 1992), Dlx2 (Liu et al, 1997), Couptf1 (Qiu et al, 1994), Er81 (Lin et al, 1998), Gsh2 (Szucsik et al, 1997), Lhx2 (Rincon-Limas et al, 1999), Lhx5 (Zhao et al, 1999), Lhx6 and Lhx7 (Grigoriou et al, 1998), Ngn2 (Gradwohl et al, 1996), Nkx2-1 (Shimamura et al, 1995), Nkx2-2 ), Nkx6-2 (Qiu et al, 1998, Pax6 (Walther and Gruss, 1991), and Shh (Echelard et al, 1993).…”

Modularity of CHIP/LDB transcription complexes regulates cell differentiation

“…24,26 aP is a LIM-homeodomain (LIM-HD) transcription factor 28 homologue of the mammalian LHX2 and LHX9. 29 CHIP and ssDP form an alternative complex (Fig. 1) together with an additional co-factor dLMo (Drosophila LIM-only), a Gata family transcription factor, PanIer (Pnr) and the β-HLH transcription factors aCHaete (aC), sCute (sC) and DauGHterLess (Da).…”

“…37 similarly, aP and its human homologue LHX2 are equally able to rescue fly ap -/-mutant phenotype and direct expression of CHIP-aP target genes in transgenic flies. 29 Mammalian ssDP proteins protect the LDB, LHX and LMo proteins from ubiquitination and subsequent proteasomemediated degradation by interfering with the interaction between LDB and the e3 ubiquitin ligase rLIM. 39,40,45 It is therefore possible that in the absence of ssDP proteins, CHIP/LDB and LMo can escape degradation by interacting with Gata and β-HLH proteins whose levels are not altered in the absence of ssDP.…”

Dynamic spatiotemporal expression of LIM genes and cofactors in the embryonic and postnatal cerebral cortex

“…Furthermore, some members display a high conservation at the functional level, such that human Lhx2 can rescue the phenotype of its Drosophila homolog, Apterous (Rincon-Limas et al, 1999). LIM-HD genes are thought to define a combinatorial code for neuronal identity in the Drosophila ventral nerve cord and in the vertebrate spinal cord (Tsuchida et al, 1994;Appel et al, 1995;Thor at el., 1999).…”