Hingole Swapnil, Verma Kritika, Chaudhary Varun
Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh, India.
Open Biol. 2025 Jan;15(7):240381. doi: 10.1098/rsob.240381. Epub 2025 Jul 2.
In the wing epithelium, canonical Wnt signalling is activated by the gradient of secreted Wingless protein (Wnt1 homolog), which interacts redundantly with the Frizzled1 and Frizzled2 receptors. While sharing overlapping functions, these receptors also have distinct non-canonical roles and exhibit differential expression patterns along the Wingless gradient. Moreover, Frizzled2, unlike Frizzled1, is thought to be essential for sustaining low-level Wingless signalling and promoting cell survival in the absence of the ligand. This raises the possibility of the two receptors acting differently along the Wingless gradient. In this study, we investigated the role of these receptors in cell survival across varying Wingless levels. We find that the loss of Frizzled2 in cells at a distance from the Wingless-producing cells-where Wingless levels are low-leads to competitive elimination of cells. In contrast, Frizzled1 is dispensable for cell survival, regardless of distance from the Wingless source. Our findings show that Frizzled2 is essential for competitive cell survival under low-Wingless conditions, and the two receptors are not equally redundant across the Wingless concentration gradient, providing insight into a mechanism for spatial and temporal precision in developmental signalling.
在翅上皮中,分泌型无翅蛋白(Wnt1同源物)的梯度激活了经典Wnt信号通路,该蛋白与卷曲蛋白1(Frizzled1)和卷曲蛋白2(Frizzled2)受体冗余相互作用。虽然这些受体具有重叠功能,但它们也具有不同的非经典作用,并且在无翅蛋白梯度上呈现出不同的表达模式。此外,与卷曲蛋白1不同,卷曲蛋白2被认为对于维持低水平的无翅蛋白信号以及在没有配体的情况下促进细胞存活至关重要。这增加了两种受体在无翅蛋白梯度上发挥不同作用的可能性。在本研究中,我们研究了这些受体在不同无翅蛋白水平下对细胞存活的作用。我们发现,在远离产生无翅蛋白的细胞(此处无翅蛋白水平较低)的细胞中,卷曲蛋白2的缺失会导致细胞的竞争性消除。相反,无论与无翅蛋白来源的距离如何,卷曲蛋白1对于细胞存活都是可有可无的。我们的研究结果表明,卷曲蛋白2在低无翅蛋白条件下对竞争性细胞存活至关重要,并且这两种受体在无翅蛋白浓度梯度上并非同等冗余,这为发育信号传导中的空间和时间精确性机制提供了见解。