Fas2: A Tale of Two Chromosomes

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, Fas2, demonstrates a mild reintegration phenotype, whereas work with the classic null allele Fas2 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: Fas2 has been used in at least 37 research articles, and Fas2 in at least three. An obvious solution is that one of the two chromosomes carries a modifier that either suppresses (Fas2) or enhances (Fas2) phenotypic severity. We find not only the latter to be the case, but identify the enhancing mutation as Nrg, also a classic null allele.