Evolutionary conservation of otd/Otx2 transcription factor action: a genome-wide microarray analysis in Drosophila

Haiqiong Montalta-He¹, Ronny Leemans¹, Thomas Loop¹, Martin Strahm², Ulrich Certa³, Michael Primig⁴, Dario Acampora⁵, Antonio Simeone⁵ and Heinrich Reichert¹

¹Institute of Zoology, Biozentrum/Pharmazentrum, Klingelbergstrasse 50, University of Basel, CH-4056 Basel, Switzerland

²Roche Bioinformatics Pharmaceuticals Division, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland

³Roche Genetics Pharmaceuticals Division, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland

⁴Biozentrum, Klingelbergstrasse 70, University of Basel, CH-4056 Basel, Switzerland

⁵MRC Centre for Developmental Neurobiology, King's College London, Guy's Campus, New Hunt's House, London SE1 1UL, UK

author email corresponding author email

Genome Biology 2002, 3:research0015.1-0015.15doi:10.1186/gb-2002-3-4-research0015


Published:	14 March 2002

Subject areas: Development, Genome studies, Genetics

Abstract

Background

Homeobox genes of the orthodenticle (otd)/Otx family have conserved roles in the embryogenesis of head and brain. Gene replacement experiments show that the Drosophila otd gene and orthologous mammalian Otx genes are functionally equivalent, in that overexpression of either gene in null mutants of Drosophila or mouse can restore defects in cephalic and brain development. This suggests that otd and Otx genes control a comparable subset of downstream target genes in either organism. Here we use quantitative transcript imaging to analyze this equivalence of otd and Otx gene action at a genomic level.

Results

Oligonucleotide arrays representing 13,400 annotated Drosophila genes were used to study differential gene expression in flies in which either the Drosophila otd gene or the human Otx2 gene was overexpressed. Two hundred and eighty-seven identified transcripts showed highly significant changes in expression levels in response to otd overexpression, and 682 identified transcripts showed highly significant changes in expression levels in response to Otx2 overexpression. Among these, 93 showed differential expression changes following overexpression of either otd or Otx2, and for 90 of these, comparable changes were observed under both experimental conditions. We postulate that these transcripts are common downstream targets of the fly otd gene and the human Otx2 gene in Drosophila.

Conclusion

Our experiments indicate that approximately one third of the otd-regulated transcripts also respond to overexpression of the human Otx2 gene in Drosophila. These common otd/Otx2 downstream genes are likely to represent the molecular basis of the functional equivalence of otd and Otx2 gene action in Drosophila.