Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA.
Laboratory of High-Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
Nat Commun. 2022 Mar 4;13(1):1185. doi: 10.1038/s41467-022-28587-z.
Asymmetric signaling and organization in the stem-cell niche determine stem-cell fates. Here, we investigate the basis of asymmetric signaling and stem-cell organization using the Drosophila wing-disc that creates an adult muscle progenitor (AMP) niche. We show that AMPs extend polarized cytonemes to contact the disc epithelial junctions and adhere themselves to the disc/niche. Niche-adhering cytonemes localize FGF-receptor to selectively adhere to the FGF-producing disc and receive FGFs in a contact-dependent manner. Activation of FGF signaling in AMPs, in turn, reinforces disc-specific cytoneme polarity/adhesion, which maintains their disc-proximal positions. Loss of cytoneme-mediated adhesion promotes AMPs to lose niche occupancy and FGF signaling, occupy a disc-distal position, and acquire morphological hallmarks of differentiation. Niche-specific AMP organization and diversification patterns are determined by localized expression and presentation patterns of two different FGFs in the wing-disc and their polarized target-specific distribution through niche-adhering cytonemes. Thus, cytonemes are essential for asymmetric signaling and niche-specific AMP organization.
不对称信号传递和干细胞龛位组织决定了干细胞命运。在这里，我们使用果蝇翅盘研究不对称信号传递和干细胞组织的基础，该翅盘产生成年肌肉祖细胞（AMP）龛位。我们表明，AMP 延伸极化纤毛与盘状上皮连接接触，并将自身附着到盘/龛位。附着在龛位上的纤毛将 FGF 受体定位，以选择性地附着到产生 FGF 的盘上，并以接触依赖的方式接收 FGF。AMP 中 FGF 信号的激活反过来又加强了盘状特异性纤毛极性/粘附，从而维持它们在盘状近端的位置。纤毛介导的粘附丧失会促使 AMP 失去龛位占据和 FGF 信号，占据盘状远端位置，并获得分化的形态特征。龛位特异性 AMP 的组织和多样化模式是由 wing-disc 中两种不同 FGF 的局部表达和呈现模式以及通过附着在龛位上的纤毛的极化靶向特异性分布决定的。因此，纤毛对于不对称信号传递和龛位特异性 AMP 组织是必不可少的。
