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


CONCLUSIONS
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.
Montalta-He
Haiqiong
H
Institute of Zoology, Biozentrum/Pharmazentrum, Klingelbergstrasse 50, University of Basel, CH-4056 Basel, Switzerland. heinrich.reichert@unibas.ch
Leemans
Ronny
R
Loop
Thomas
T
Strahm
Martin
M
Certa
Ulrich
U
Primig
Michael
M
Acampora
Dario
D
Simeone
Antonio
A
Reichert
Heinrich
H
D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D004625:Embryo, Nonmammalian; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D016678:Genome; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051857:Otx Transcription Factors; D012333:RNA, Messenger / Q000096:biosynthesis / Q000145:classification; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; D012333:RNA, Messenger; D015534:Trans-Activators; C093053:oc protein, Drosophila