GENETIC REGULATION OF THE DEVELOPMENT OF A MALE SPECIFIC MUSCLE IN DROSOPHILA

这里提出的工作可能会深入了解一般机制 潜在的肌肉发育和分化。 的关键特征 肌肉的发育是与发育中的神经系统相互作用的。 任何 促进对正常相互依存关系的理解， 肌肉和神经的发育可能最终导致 研究人类神经肌肉疾病。 这个实验模型 研究将是果蝇中的fruitless（fru）基因。 该基因的突变提示了fru基因产物的可能作用 在：（a）发育中的神经系统-突变的成年男性无法 处理求偶刺激线索正确导致他们的异常 其他雄性的求爱;和（B）肌肉发育--突变的成年雄性 未能发展一个大的，成对的肌肉，通常出现在第五 腹部部分（“劳伦斯肌肉”）。 解开这些 fru在果蝇发育过程中的多效性取决于其分子 克隆和鉴定其产物。 的起点 为实现这一目标而设计的实验将是鉴定的cDNA，其 对应于FRU细胞遗传学位置。 该cDNA和相关探针将 用于鉴定与fru相关的基因组序列， 果蝇一生中fru的表达模式。 接下来-- 最重要的是--目标将是在fru中识别这些序列 其在成年男性肌肉分化中起作用。 在这里，一个独特的 方法提出。 许多果蝇物种不能区分 成年男性的劳伦斯肌肉作为标准-这包括物种 甚至和黑腹果蝇属于同一个物种亚群。 因此 fru作为肌肉发育的调节器的作用可能是“获得 功能，”或遗传添加，这个基因，因为它存在于D。 黑腹菌 如果是这样，这些序列，无论是调节性的还是蛋白质- 编码，将通过消减杂交方法鉴定。 最后，fru作为肌肉调节器的机制 分化可能是进化上保守的。 为了验证这一 可能性，fru同源序列将在小鼠中筛选 基因组和胚胎cDNA文库。

Work proposed here will likely yield insight into the general mechanisms underlying muscle development and differentiation. A critical feature of muscle development is interaction with the developing nervous system. Any advance in the understanding of the normal interdependence between developing muscles and nerves might ultimately lead to progress in the study of human neuromuscular disease. The experimental model in this study will be the fruitless (fru) gene in Drosophila melanogaster. Mutation of this gene has suggested probable roles for a fru gene product in: (a) the developing nervous system--mutant adult males are unable to process courtship-stimulating cues properly leading to their aberrant courtship of other males; and (b) muscle development--mutant adult males fail to develop a large, paired muscle which normally appears in the fifth abdominal segment (the "Muscle of Lawrence"). Unraveling these pleiotropic effects of fru during fly development hinges on its molecular cloning and identification of its product(s). The starting point for experiments designed to achieve this goal will be an identified cDNA which maps to the fru cytogenetic location. This cDNA and related probes will be used to identify genomic sequences relevant to fru, and to provide data on the expression pattern of fru during the life of the fly. The next-- and most important--goal will be to identify those sequences within fru which play a role in adult male muscle differentiation. Here, a unique approach is proposed. Many Drosophila species fail to differentiate the Muscle of Lawrence in adult males as the norm--this includes species belonging even to the same species subgroup as melanogaster. Thus the role of fru as a regulator of muscle development may be a "gain of function," or genetic addition, to this gene as it exists in D. melanogaster. If so, such sequences, whether regulatory or protein- encoding, will be identified by subtractive hybridization methods. Finally, the mechanism by which fru serves as a regulator of muscle differentiation may be evolutionarily conserved. To test this possibility, fru-homologous sequences will be screened for in murine genomic and embryonic cDNA libraries.