Department of Biology, University of Rochester, Rochester, NY 14627, USA.
Division of Biological Sciences, University of Missouri, Columbia, MO 65203, USA.
G3 (Bethesda). 2024 May 7;14(5). doi: 10.1093/g3journal/jkae047.
The cell-cell adhesion molecule Fasciclin II (Fas2) has long been studied for its evolutionarily conserved role in axon guidance. It is also expressed in the follicular epithelium, where together with a similar protein, Neuroglian (Nrg), it helps to drive the reintegration of cells born out of the tissue plane. Remarkably, one Fas2 protein null allele, Fas2G0336, demonstrates a mild reintegration phenotype, whereas work with the classic null allele Fas2EB112 showed more severe epithelial disorganization. These observations raise the question of which allele (if either) causes a bona fide loss of Fas2 protein function. The problem is not only relevant to reintegration but fundamentally important to understanding what this protein does and how it works: Fas2EB112 has been used in at least 37 research articles, and Fas2G0336 in at least three. An obvious solution is that one of the two chromosomes carries a modifier that either suppresses (Fas2G0336) or enhances (Fas2EB112) phenotypic severity. We find not only the latter to be the case, but identify the enhancing mutation as Nrg14, also a classic null allele.
细胞间黏附分子 Fasciclin II（Fas2）长期以来因其在轴突导向中的进化保守作用而受到研究。它也在滤泡上皮细胞中表达，与类似的蛋白 Neuroglian（Nrg）一起，它有助于驱动组织平面外产生的细胞的再整合。值得注意的是，一个 Fas2 蛋白缺失等位基因 Fas2G0336 表现出轻微的再整合表型，而经典的缺失等位基因 Fas2EB112 的研究表明上皮组织更严重的紊乱。这些观察结果提出了一个问题，即哪个等位基因（如果有的话）导致 Fas2 蛋白功能的真正丧失。这个问题不仅与再整合有关，而且对理解该蛋白的功能及其工作方式至关重要：Fas2EB112 至少被用于 37 篇研究文章，Fas2G0336 至少被用于三篇。一个明显的解决方案是两个染色体中的一个携带一个修饰基因，它要么抑制（Fas2G0336）要么增强（Fas2EB112）表型严重程度。我们发现不仅存在后者，而且还确定增强突变是 Nrg14，它也是一个经典的缺失等位基因。
