The Section of Molecular Cell and Developmental Biology and the Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America.
PLoS One. 2012;7(4):e35365. doi: 10.1371/journal.pone.0035365. Epub 2012 Apr 6.
Adult stem cells must balance self-renewal and differentiation for tissue homeostasis. The Drosophila ovary has provided a wealth of information about the extrinsic niche signals and intrinsic molecular processes required to ensure appropriate germline stem cell renewal and differentiation. The factors controlling behavior of the more recently identified follicle stem cells of the ovary are less well-understood but equally important for fertility. Here we report that translational regulators play a critical role in controlling these cells. Specifically, the translational regulator Caprin (Capr) is required in the follicle stem cell lineage to ensure maintenance of this stem cell population and proper encapsulation of developing germ cells by follicle stem cell progeny. In addition, reduction of one copy of the gene fmr1, encoding the translational regulator Fragile X Mental Retardation Protein, exacerbates the Capr encapsulation phenotype, suggesting Capr and fmr1 are regulating a common process. Caprin was previously characterized in vertebrates as Cytoplasmic Activation/Proliferation-Associated Protein. Significantly, we find that loss of Caprin alters the dynamics of the cell cycle, and we present evidence that misregulation of CycB contributes to the disruption in behavior of follicle stem cell progeny. Our findings support the idea that translational regulators may provide a conserved mechanism for oversight of developmentally critical cell cycles such as those in stem cell populations.
成体干细胞必须在自我更新和分化之间保持平衡，以维持组织内稳态。果蝇卵巢为确保生殖干细胞的适当更新和分化所必需的外在生态位信号和内在分子过程提供了丰富的信息。调控新发现的卵巢滤泡干细胞行为的因素了解较少，但对生育能力同样重要。在这里，我们报告翻译调节因子在控制这些细胞方面起着关键作用。具体来说，翻译调节因子 Caprin（Capr）在滤泡干细胞谱系中是必需的，以确保该干细胞群体的维持以及滤泡干细胞后代对发育中的生殖细胞的适当包裹。此外，降低编码翻译调节因子 Fragile X 智力迟钝蛋白的基因 fmr1 的一个拷贝会加剧 Capr 包裹表型，这表明 Capr 和 fmr1 正在调节一个共同的过程。Caprin 之前在脊椎动物中被描述为细胞质激活/增殖相关蛋白。重要的是，我们发现 Caprin 的缺失改变了细胞周期的动态，并且我们提供了证据表明 CycB 的失调导致了滤泡干细胞后代行为的中断。我们的发现支持了这样一种观点，即翻译调节因子可能为监督发育关键细胞周期（如干细胞群体中的细胞周期）提供一种保守的机制。
