Montalta-He Haiqiong, Leemans Ronny, Loop Thomas, Strahm Martin, Certa Ulrich, Primig Michael, Acampora Dario, Simeone Antonio, Reichert Heinrich
Institute of Zoology, Biozentrum/Pharmazentrum, Klingelbergstrasse 50, University of Basel, CH-4056 Basel, Switzerland.
Genome Biol. 2002;3(4):RESEARCH0015. doi: 10.1186/gb-2002-3-4-research0015. Epub 2002 Mar 14.
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.
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.
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.
正齿科（otd）/Otx家族的同源异型盒基因在头部和脑部的胚胎发育中具有保守作用。基因替代实验表明，果蝇otd基因和哺乳动物直系同源Otx基因在功能上是等效的，因为在果蝇或小鼠的无效突变体中过表达这两种基因中的任何一种都可以恢复头部和脑部发育的缺陷。这表明otd和Otx基因在任一生物体中控制着相当一部分下游靶基因。在此，我们使用定量转录成像在基因组水平上分析otd和Otx基因作用的这种等效性。
使用代表13400个注释果蝇基因的寡核苷酸阵列来研究果蝇中果蝇otd基因或人类Otx2基因过表达时的差异基因表达。287个鉴定出的转录本显示出对otd过表达的反应中表达水平有高度显著变化，682个鉴定出的转录本显示出对Otx2过表达的反应中表达水平有高度显著变化。其中，93个在otd或Otx2过表达后显示出差异表达变化，并且其中90个在两种实验条件下都观察到了类似的变化。我们推测这些转录本是果蝇中果蝇otd基因和人类Otx2基因共同的下游靶标。
我们的实验表明，约三分之一受otd调控的转录本在果蝇中也对人类Otx2基因的过表达有反应。这些otd/Otx2共同的下游基因可能代表了果蝇中otd和Otx2基因作用功能等效性的分子基础。
