Grens A, Mason E, Marsh J L, Bode H R
Developmental Biology Center, University of California, Irvine 92717, USA.
Development. 1995 Dec;121(12):4027-35. doi: 10.1242/dev.121.12.4027.
Members of the Achaete-scute family of basic helix-loop-helix transcription factors are involved in cell fate specification in vertebrates and invertebrates. We have isolated and characterized a cnidarian achaete-scute homolog, CnASH, from Hydra vulgaris, a representative of an evolutionarily ancient branch of metazoans. There is a single achaete-scute gene in Hydra, and the bHLH domain of the predicted gene product shares a high degree of amino acid sequence similarity with those of vertebrate and Drosophila Achaete-scute proteins. In Hydra, CnASH is expressed in a subset of the interstitial cells as well as differentiation intermediates of the nematocyte pathways. In vitro translated CnASH protein can form heterodimers with the Drosophila bHLH protein Daughterless, and these dimers bind to consensus Achaete-scute DNA binding sites in a sequence-specific manner. Ectopic expression of CnASH in wild-type late third instar Drosophila larvae and early pupae leads to the formation of ectopic sensory organs, mimicking the effect of ectopic expression of the endogenous achaete-scute genes. Expression of CnASH in flies that are achaete and scute double mutants gives partial rescue of the mutant phenotype, comparable to the degree of rescue obtained by ectopic expression of the Drosophila genes. These results indicate that the achaete-scute type of bHLH genes for cell fate specification, as well as their mode of action, arose early and have been conserved during metazoan evolution.
碱性螺旋-环-螺旋转录因子的Achaete-scute家族成员参与脊椎动物和无脊椎动物的细胞命运特化。我们从多细胞动物进化古老分支的代表物种——普通水螅中分离并鉴定了一种刺胞动物的achaete-scute同源物CnASH。水螅中存在单个achaete-scute基因，预测的基因产物的bHLH结构域与脊椎动物和果蝇的Achaete-scute蛋白的氨基酸序列具有高度相似性。在水螅中，CnASH在间质细胞的一个亚群以及刺细胞途径的分化中间体中表达。体外翻译的CnASH蛋白可以与果蝇bHLH蛋白无女儿形成异源二聚体，并且这些二聚体以序列特异性方式结合到共有Achaete-scute DNA结合位点。在野生型果蝇三龄晚期幼虫和早期蛹中异位表达CnASH会导致异位感觉器官的形成，这与内源性achaete-scute基因异位表达的效果相似。在achaete和scute双突变体果蝇中表达CnASH可部分挽救突变体表型，其程度与果蝇基因异位表达所获得的挽救程度相当。这些结果表明，用于细胞命运特化的achaete-scute类型的bHLH基因及其作用模式在多细胞动物进化早期就已出现并得以保守。
