Chau Johnnie, Kulnane Laura Shapiro, Salz Helen K
Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4955, USA.
Genetics. 2009 May;182(1):121-32. doi: 10.1534/genetics.109.100693. Epub 2009 Feb 23.
In Drosophila, the female-specific SEX-LETHAL (SXL) protein is required for oogenesis, but how Sxl interfaces with the genetic circuitry controlling oogenesis remains unknown. Here we use an allele of sans fille (snf) that specifically eliminates SXL protein in germ cells to carry out a detailed genetic and cell biological analysis of the resulting ovarian tumor phenotype. We find that tumor growth requires both Cyclin B and zero population growth, demonstrating that these mutant cells retain at least some of the essential growth-control mechanisms used by wild-type germ cells. Using a series of molecular markers, we establish that while the tumor often contains at least one apparently bona fide germline stem cell, the majority of cells exhibit an intermediate fate between a stem cell and its daughter cell fated to differentiate. In addition, snf tumors misexpress a select group of testis-enriched markers, which, remarkably, are also misexpressed in ovarian tumors that arise from the loss of bag of marbles (bam). Results of genetic epistasis experiments further reveal that bam's differentiation-promoting function depends on Sxl. Together these data demonstrate a novel role for Sxl in the lineage progression from stem cell to committed daughter cell and suggest a model in which Sxl partners with bam to facilitate this transition.
在果蝇中,雌性特异性的性别致死(SEX-LETHAL,SXL)蛋白对于卵子发生是必需的,但Sxl如何与控制卵子发生的遗传通路相互作用仍不清楚。在这里,我们使用一个无女儿(sans fille,snf)的等位基因,该等位基因能特异性消除生殖细胞中的SXL蛋白,以便对由此产生的卵巢肿瘤表型进行详细的遗传学和细胞生物学分析。我们发现肿瘤生长需要细胞周期蛋白B和零种群增长,这表明这些突变细胞至少保留了野生型生殖细胞所使用的一些基本生长控制机制。使用一系列分子标记,我们确定,虽然肿瘤通常至少含有一个明显真正的生殖系干细胞,但大多数细胞表现出介于干细胞及其注定分化的子细胞之间的中间命运。此外,snf肿瘤错误表达了一组睾丸富集标记,值得注意的是,这些标记在因失去大理石袋(bag of marbles,bam)而产生的卵巢肿瘤中也有错误表达。遗传上位性实验结果进一步表明,bam的促进分化功能依赖于Sxl。这些数据共同证明了Sxl在从干细胞到定向子细胞的谱系进展中的新作用,并提出了一个模型,即Sxl与bam合作以促进这种转变。