Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY 10016, USA.
Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY 10016, USA; Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Curr Biol. 2020 Feb 24;30(4):708-714.e4. doi: 10.1016/j.cub.2019.12.021. Epub 2020 Jan 30.
Niche cells often wrap membrane extensions around stem cell surfaces. Niche wrapping has been proposed to retain stem cells in defined positions and affect signaling [e.g., 1, 2]. To test these hypotheses and uncover additional functions of wrapping, we investigated niche wrapping of primordial germ cells (PGCs) in the C. elegans embryonic gonad primordium. The gonad primordium contains two PGCs that are wrapped individually by two somatic gonad precursor cells (SGPs). SGPs are known to promote PGC survival during embryogenesis and exit from quiescence after hatching, although how they do so is unknown [3]. Here, we identify two distinct functions of SGP wrapping that are critical for PGC quiescence and survival. First, niche cell wrapping templates a laminin-based basement membrane around the gonad primordium. Laminin and the basement membrane receptor dystroglycan function to maintain niche cell wrapping, which is critical for normal gonad development. We find that laminin also preserves PGC quiescence during embryogenesis. Exit from quiescence following laminin depletion requires glp-1/Notch and is accompanied by inappropriate activation of the GLP-1 target sygl-1 in PGCs. Independent of basement membrane, SGP wrapping performs a second, crucial function to ensure PGC survival. Endodermal cells normally engulf and degrade large lobes extended by the PGCs [4]. When SGPs are absent, we show that endodermal cells can inappropriately engulf and cannibalize the PGC cell body. Our findings demonstrate how niche cell wrapping protects germ cells by manipulating their signaling environment and by shielding germ cells from unwanted cellular interactions that can compromise their survival.
龛细胞通常将膜延伸物包裹在干细胞表面周围。龛包裹被认为可以将干细胞保留在特定位置并影响信号转导[例如,1,2]。为了测试这些假设并发现包裹的其他功能,我们研究了秀丽隐杆线虫胚胎性腺原基中原始生殖细胞(PGC)的龛包裹。性腺原基包含两个被两个体腔性腺前体细胞(SGPs)分别包裹的 PGC。尽管尚不清楚它们是如何做到这一点的,但已知 SGPs 在胚胎发生过程中促进 PGC 的存活并在孵化后退出静止状态[3]。在这里,我们确定了 SGP 包裹对 PGC 静止和存活至关重要的两个不同功能。首先,龛细胞包裹为性腺原基周围的层粘连蛋白为基础的基底膜提供模板。层粘连蛋白和基底膜受体 dystroglycan 用于维持龛细胞包裹,这对于正常的性腺发育至关重要。我们发现层粘连蛋白也可以在胚胎发生过程中维持 PGC 静止。层粘连蛋白耗尽后从静止中退出需要 glp-1/Notch,并伴随着 PGC 中 GLP-1 靶标 sygl-1 的不当激活。与基底膜无关,SGP 包裹执行第二个关键功能,以确保 PGC 的存活。内胚层细胞通常吞噬和降解 PGC 延伸的大叶[4]。当 SGPs 不存在时,我们表明内胚层细胞可以不当吞噬和吞噬 PGC 细胞体。我们的发现表明龛细胞包裹如何通过操纵其信号环境并保护生殖细胞免受可能损害其存活的不需要的细胞相互作用来保护生殖细胞。