RESUMO
Drosophila thoracic muscles are comprised of both direct flight muscles (DFMs) and indirect flight muscles (IFMs). The IFMs can be further subdivided into dorsolongitudinal muscles (DLMs) and dorsoventral muscles (DVMs). The correct patterning of each category of muscles requires the coordination of specific executive regulatory programs. DFM development requires key regulatory genes such as cut (ct) and apterous (ap), whereas IFM development requires vestigial (vg). Using a new vg(null) mutant, we report that a total absence of vg leads to DLM degeneration through an apoptotic process and to a total absence of DVMs in the adult. We show that vg and scalloped (sd), the only known VG transcriptional coactivator, are coexpressed during IFM development. Moreover, we observed an ectopic expression of ct and ap, two markers of DFM development, in developing IFMs of vg(null) pupae. In addition, in vg(null) adult flies, degenerating DLMs express twist (twi) ectopically. We provide evidence that ap ectopic expression can induce per se ectopic twi expression and muscle degeneration. All these data seem to indicate that, in the absence of vg, the IFM developmental program switches into the DFM developmental program. Moreover, we were able to rescue the muscle phenotype of vg(null) flies by using the activity of ap promoter to drive VG expression. Thus, vg appears to be a key regulatory gene of IFM development.
Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Músculos/fisiologia , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Células Cultivadas , Proteínas de Drosophila/genética , Proteínas de Homeodomínio/genética , Proteínas com Homeodomínio LIM , Masculino , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/fisiologia , Músculos/metabolismo , Músculos/patologia , Mutação , Mioblastos/fisiologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Proteína 1 Relacionada a Twist , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/fisiologiaRESUMO
The twist gene has been characterized for its role in myogenesis in several species. In addition, in mammalian cultured cells, it has been shown that twist is a potential oncogene antagonizing p53-dependent apoptosis. To study, in vivo, the role of twist in apoptosis and proliferation, we constructed transgenic Drosophila lines allowing ectopic expression of different twist orthologs. We report that: (i) Drosophila twist induces apoptosis and activates the reaper promoter, (ii) nematode twist induces arrest of proliferation without apoptosis, and (iii) human twist retains its potentialities observed in mammalian cultured cells and antagonizes Drosophila p53-dependent apoptosis. In addition, we show that human twist is able to induce cell proliferation in Drosophila. Data suggest that the pathway by which human twist antagonizes Drosophila p53 could be conserved. These transgenic lines thus constitute a powerful tool to identify targets and modifiers of human twist.
Assuntos
Apoptose/fisiologia , Drosophila melanogaster/metabolismo , Proteínas Nucleares/genética , Animais , Animais Geneticamente Modificados , Proteínas de Caenorhabditis elegans/genética , Divisão Celular/fisiologia , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Humanos , Fator de Crescimento Insulin-Like I/genética , Modelos Biológicos , Fenótipo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética , Proteína 1 Relacionada a TwistRESUMO
An approximately 1.3-kb region including the rp49 gene plus its 5' and 3' flanking regions was sequenced in 24 lines of Drosophila simulans (10 from Spain and 14 from Mozambique). Fifty-four nucleotide and 8 length polymorphisms were detected. All nucleotide polymorphisms were silent: 52 in noncoding regions and 2 at synonymous sites in the coding region. Estimated silent nucleotide diversity was similar in both populations (pi = 0.016, for the total sample). Nucleotide variation revealed an unusual haplotype structure showing a subset of 11 sequences with a single polymorphism. This haplotype was present at intermediate frequencies in both the European and the African samples. The presence of such a major haplotype in a highly recombining region is incompatible with the neutral equilibrium model. This haplotype structure in both a derived and a putatively ancestral population can be most parsimoniously explained by positive selection. As the rate of recombination in the rp49 region is high, the target of selection should be close to or within the region studied.
