Cline T W
Genetics. 1986 Jul;113(3):641-63. doi: 10.1093/genetics/113.3.641.
Characterization of a partial-loss-of-function, female-specific lethal mutation has identified an X-linked genetic element (1-34.3; 10B4) that functions as a positive regulator of Sxl, a central gene controlling sex determination in Drosophila melanogaster. The name, sisterless-a, was chosen both to suggest functional similarities that exist between this gene and another positive regulator of Sxl, the maternally acting gene daughterless (da), and also to highlight an important difference; namely, that in contrast to da, it is the zygotic rather than maternal functioning of sis-a that is involved in its interaction with Sxl. As with da, the female-specific lethal phenotype of sis-a is suppressed both by SxlM#1, a gain-of-function mutant allele of the target gene, and, to a lesser extent, by a duplication of Sxl+. Mutations at sis-a, da and Sxl display female-specific dominant synergism, each enhancing the others' lethal effects. The allele specificity with respect to Sxl of these dominant interactions indicates that sis-a and da affect the same aspect of Sxl regulation. As with previous studies of da and Sxl, the masculinizing effects of loss of sis-a function are generally obscured by lethal effects, presumably related to upsets in dosage compensation. The masculinizing effects can be dissociated from lethal effects by analysis of triploid intersexes (XX AAA) or by analysis of diploid females who are also mutant for autosomal genes known to be required for the transcriptional hyperactivation associated with dosage compensation in males. Analysis of foreleg development shows that intersexuality generated by sis-a is of the mosaic type: At the level of individual cells, only male or female development is observed, never an intermediate sexual phenotype characteristic of true intersexes. Sexual development of diplo-X germline and somatic clones of sis-a tissue generated by mitotic recombination during larval stages is normal, as is the sexual phenotype of homozygous sis-a escapers. Considered in their totality, these results indicate that sis-a functions early in development to help establish the activity state of Sxl and thereby initiate the sexual pathway commitment, rather than functioning later in the processes by which Sxl maintains and expresses the sex determination decision.
对一种功能部分丧失、雌性特异性致死突变的特性分析，鉴定出一个X连锁遗传元件（1-34.3；10B4），它作为Sex-lethal（Sxl）的正向调节因子发挥作用，Sxl是控制黑腹果蝇性别决定的核心基因。之所以选择“无姐妹-a”（sisterless-a）这个名字，一方面是为了表明该基因与另一个Sxl的正向调节因子、母源作用基因“无女儿”（daughterless，da）之间存在功能相似性，另一方面也是为了突出一个重要差异；即，与da不同，sis-a与Sxl相互作用时涉及的是合子而非母源功能。与da一样，sis-a的雌性特异性致死表型既受到目标基因功能获得性突变等位基因SxlM#1的抑制，也在较小程度上受到Sxl+重复的抑制。sis-a、da和Sxl处的突变表现出雌性特异性显性协同作用，彼此增强对方的致死效应。这些显性相互作用相对于Sxl的等位基因特异性表明，sis-a和da影响Sxl调节的同一方面。与之前对da和Sxl的研究一样，sis-a功能丧失的雄性化效应通常被致死效应掩盖，推测这与剂量补偿失调有关。通过分析三倍体间性体（XX AAA）或分析也是与雄性剂量补偿相关的转录超激活所需常染色体基因突变体的二倍体雌性，可以将雄性化效应与致死效应分离。前腿发育分析表明，sis-a产生的间性是镶嵌型的：在单个细胞水平上，只观察到雄性或雌性发育，从未出现真正间性体特有的中间性表型。幼虫阶段通过有丝分裂重组产生的sis-a组织的双X生殖系和体细胞克隆的性发育正常，纯合sis-a逃逸者的性表型也是如此。综合考虑这些结果表明，sis-a在发育早期发挥作用，以帮助建立Sxl的活性状态，从而启动性别途径的决定，而不是在Sxl维持和表达性别决定的过程后期发挥作用。
