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

Conservation of the expression and function of apterous orthologs in Drosophila and mammals.
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DOI:
10.1073/pnas.96.5.2165
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发表时间:
1999-03
影响因子:
11.1
通讯作者:
D. Rincon-Limas;C. Lu;I. Canal;M. Calleja;C. Rodríguez-Esteban;J. Izpisúa-Belmonte;J. Botas
D. Rincon-Limas;C. Lu;I. Canal;M. Calleja;C. Rodríguez-Esteban;J. Izpisúa-Belmonte;J. Botas
中科院分区:
综合性期刊1区
文献类型:
--
作者:
D. Rincon-Limas;C. Lu;I. Canal;M. Calleja;C. Rodríguez-Esteban;J. Izpisúa-Belmonte;J. Botas

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果蝇AP基因编码LIM同源结构域家族的一种蛋白。许多这类转录因子在进化过程中是保守的;然而,其结构保守的功能意义通常尚不清楚。AP最为人所知的是其作为背部选择基因的基本作用,它是翅膀形成和生长所必需的,但它也有其他重要的功能,对于神经元的束征、生育和正常生存是必需的。我们分离了小鼠(MLhx2)和人(HLhx2)AP同源基因,并使用转基因动物和挽救实验来研究AP蛋白在进化过程中的保守性。我们发现,人类蛋白LHX2能够正确调控果蝇中的AP靶基因,在异位生产时引起与AP相同的表型,最重要的是,拯救AP突变表型的效率与苍蝇蛋白一样高。此外,我们发现果蝇和老鼠基因的表达模式有惊人的相似之处。MLhx2和AP分别在神经索、眼、嗅器官、脑和四肢表达。这些结果表明AP蛋白的功能在整个门中是保守的,并认为其表达模式的某些方面也是从昆虫和脊椎动物的共同祖先那里保守下来的。
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.