EVOLUTIONARY CONSERVATION OF A CELL FATE SPECIFICATION GENE - THE HYDRA ACHAETE-SCUTE HOMOLOG HAS PRONEURAL ACTIVITY IN DROSOPHILA

Members of the Achaete-scute family of basic helix-loop-helix transcri ption factors are involved in cell fate specification in vertebrates a nd invertebrates, We have isolated and characterized a cnidarian achae te-scute homolog, CnASH, from Hydra vulgaris, a representative of an e volutionarily ancient branch of metazoans. There is a single achaete-s cute gene in Hydra, and the bHLH domain of the predicted gene product shares a high degree of amino acid sequence similarity with those of v ertebrate and Drosophila Achaete-scute proteins. In Hydra, CnASH is ex pressed in a subset of the interstitial cells as well as differentiati on intermediates of the nematocyte pathways. In vitro translated CnASH protein can form heterodimers with the Drosophila bHLH protein Daught erless, and these dimers bind to consensus Achaete-scute DNA binding s ites in a sequence-specific manner. Ectopic expression of CnASH in wil d-type late third instar Drosophila larvae and early pupae leads to th e 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 resc ue of the mutant phenotype, comparable to the degree of rescue obtaine d by ectopic expression of the Drosophila genes, These results indicat e that the achaete-scute type of bHLH genes for cell fate specificatio n, as well as their mode of action, arose early and have been conserve d during metazoan evolution.