Leuzinger S, Hirth F, Gerlich D, Acampora D, Simeone A, Gehring W J, Finkelstein R, Furukubo-Tokunaga K, Reichert H
Zoological Institute, University of Basel, Basel, Switzerland.
Development. 1998 May;125(9):1703-10. doi: 10.1242/dev.125.9.1703.
Members of the orthodenticle gene family are essential for embryonic brain development in animals as diverse as insects and mammals. In Drosophila, mutational inactivation of the orthodenticle gene results in deletions in anterior parts of the embryonic brain and in defects in the ventral nerve cord. In the mouse, targeted elimination of the homologous Otx2 or Otx1 genes causes defects in forebrain and/or midbrain development. To determine the morphogenetic properties and the extent of evolutionary conservation of the orthodenticle gene family in embryonic brain development, genetic rescue experiments were carried out in Drosophila. Ubiquitous overexpression of the orthodenticle gene rescues both the brain defects and the ventral nerve cord defects in orthodenticle mutant embryos; morphology and nervous system-specific gene expression are restored. Two different time windows exist for the rescue of the brain versus the ventral nerve cord. Ubiquitous overexpression of the human OTX1 or OTX2 genes also rescues the brain and ventral nerve cord phenotypes in orthodenticle mutant embryos; in the brain, the efficiency of morphological rescue is lower than that obtained with overexpression of orthodenticle. Overexpression of either orthodenticle or the human OTX gene homologs in the wild-type embryo results in ectopic neural structures. The rescue of highly complex brain structures in Drosophila by either fly or human orthodenticle gene homologs indicates that these genes are interchangeable between vertebrates and invertebrates and provides further evidence for an evolutionarily conserved role of the orthodenticle gene family in brain development.
正齿科基因家族的成员对于昆虫和哺乳动物等多种动物的胚胎脑发育至关重要。在果蝇中，正齿科基因的突变失活会导致胚胎脑前部缺失以及腹侧神经索出现缺陷。在小鼠中，同源的Otx2或Otx1基因的靶向消除会导致前脑和/或中脑发育缺陷。为了确定正齿科基因家族在胚胎脑发育中的形态发生特性和进化保守程度，在果蝇中进行了基因拯救实验。正齿科基因的普遍过表达挽救了正齿科突变胚胎中的脑缺陷和腹侧神经索缺陷；形态和神经系统特异性基因表达得以恢复。挽救脑和腹侧神经索存在两个不同的时间窗口。人OTX1或OTX2基因的普遍过表达也挽救了正齿科突变胚胎中的脑和腹侧神经索表型；在脑中，形态挽救的效率低于正齿科基因过表达所获得的效率。在野生型胚胎中过表达正齿科基因或人OTX基因同源物会导致异位神经结构。果蝇的正齿科基因同源物或人正齿科基因同源物对高度复杂脑结构的挽救表明，这些基因在脊椎动物和无脊椎动物之间是可互换的，并为正齿科基因家族在脑发育中具有进化保守作用提供了进一步的证据。
