Gpr125, encoded by Adgra3, is an orphan adhesion G-protein coupled receptor (aGPCR) implicated in Wnt signaling and planar polarity. Here we establish both physiological and pathological roles for Gpr125. We show that mice lacking Gpr125 or its signaling domains display an ocular phenotype with many hallmarks of human dry eye syndrome. These include squinting, abnormal lacrimation, mucus accumulation, swollen eyelids and inflammatory infiltration of lacrimal and meibomian glands. Utilizing a Gpr125-β-gal reporter and scRNAseq, we identify Gpr125 expression in a discrete population of cells located at the tips of migrating embryonic lacrimal ducts.By lineage tracing we show these cells function as progenitors of the adult lacrimal myoepithelium. Beyond defining an essential role for Gpr125 in tear film and identifying its utility as a marker of lacrimal progenitors, this study implicates Gpr125 in the etiology of blepharitis and dry eye syndrome, and defines novel animal models of these common maladies.

中文翻译：

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Gpr125可识别泪道尖端的肌上皮祖细胞，对于泪膜必不可少。

Gpr125，由Adgra3编码是一种孤儿粘附G蛋白偶联受体（aGPCR），与Wnt信号传导和平面极性有关。在这里，我们建立了Gpr125的生理和病理作用。我们显示缺少Gpr125或其信号域的小鼠显示出具有人类干眼症候群的许多标志的眼表型。这些包括include眼，流泪异常，粘液积聚，眼睑肿胀以及泪腺和睑板腺的炎性浸润。利用Gpr125-β-gal报告基因和scRNAseq，我们在迁移的胚胎泪管末端的离散细胞群中鉴定了Gpr125的表达。通过谱系追踪，我们显示这些细胞起着成人泪道肌上皮祖细胞的作用。除了定义Gpr125在泪膜中的重要作用并确定其作为泪祖细胞标记物的用途外，