Abstract:
Stem cell maintenance and differentiation can be regulated via the differential activity of transcription factors within stem cells and their progeny. For these factors to be active, they need to be transported from their site of synthesis in the cytoplasm into the nucleus. A tissue-specific requirement for factors involved in nuclear importation is a potential mechanism to regulate stem cell differentiation. We have undertaken a characterization of male sterile importin alpha 1 (Dα1) null alleles in Drosophila and found that Dα1 is required for maintaining germline stem cells (GSCs) in the testis niche. The loss of GSCs can be rescued by ectopic expression of Dα1 within the germline but the animals are still infertile, indicating a second role for Dα1 in spermatogenesis. Expression of a Dα1 dominant negative transgene in GSCs confirmed a functional requirement for Dα1 in GSC maintenance but expression of the transgene in differentiating spermatogonia did not exhibit a phenotype indicating a specific role for Dα1 within GSCs. Our data indicate that Dα1 is utilized as a regulatory protein within GSCs to facilitate nuclear importation of proteins that maintain the stem cell pool.
摘要:
干细胞维持和分化可以通过干细胞及其后代中转录因子的差异活性来调节。为了使这些因素活跃起来,它们需要从细胞质中的合成位点运输到细胞核中。对参与核输入的因子的组织特异性要求是调节干细胞分化的潜在机制。我们已经对果蝇中的雄性不育输入蛋白α1(Dα1)无效等位基因进行了表征,发现Dα1是维持睾丸生态位中的种系干细胞(GSC)所必需的。GSC的丢失可以通过Dα1在种系内的异位表达来挽救,但动物仍然不育,表明Dα1在精子发生中的第二个作用。GSC中Dα1显性阴性转基因的表达证实了在GSC维持中对Dα1的功能要求,但在分化精原细胞中转基因的表达未表现出表明Dα1在GSC中的特定作用的表型。我们的数据表明,Dα1被用作GSC内的调节蛋白,以促进维持干细胞库的蛋白的核输入。