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

这里提出的工作可能会对一般机制有深入的了解。 潜在的肌肉发育和分化。的一个重要特征 肌肉发育是与发育中的神经系统相互作用的过程。任何 对人与人之间正常相互依赖关系的认识进展 肌肉和神经的发育可能最终会导致 人类神经肌肉疾病的研究。其中的实验模型 将对果蝇的无果(Fru)基因进行研究。 该基因的突变提示可能与一个fru基因产物有关。 在：(A)发育中的神经系统--突变的成年男性无法 恰当地处理刺激求偶的线索会导致它们的异常 其他雄性的求爱；和(B)肌肉发育--突变的成年雄性 没有发育出通常出现在第五节的大的成对的肌肉 腹段(劳伦斯肌)。解开这些 果糖在果蝇发育过程中的多效性与其分子水平有关 其产物的克隆和鉴定(S)。的起点 为实现这一目标而设计的实验将是一种经鉴定的 映射到FRU细胞遗传学位置。该cDNAs和相关探针将 用于鉴定与FRU相关的基因组序列，并提供数据 果蝇生命周期中fRU的表达模式。下一个-- 最重要的是，目标将是识别FRU中的这些序列 它们在成年男性肌肉分化中起作用。在这里，一个独特的 提出了解决这一问题的方法。许多果蝇物种无法区分 成年男性的劳伦斯肌肉作为标准--这包括物种 甚至与黑腹鱼属于同一物种亚群。因此， FRU作为肌肉发育的调节器的作用可能是“获得 功能，“或遗传附加，因为它存在于D。 黑猩猩。如果是这样的话，这样的序列，无论是调控序列还是蛋白质序列- 编码，将通过消减杂交方法进行鉴定。 最后，FRU作为肌肉调节器的机制 分化可能在进化上是保守的。为了测试这一点 有可能，将在小鼠身上筛选出四个同源序列 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.