Fas2^EB112: 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^G0336, demonstrates a mild reintegration phenotype, whereas work with the classic null alleleFas2^EB112showed more severe epithelial disorganization. These observations raise the question of which allele (if either) causes abona fideloss 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^EB112has been used in at least 37 research articles, andFas2^G0336in at least three. An obvious solution is that one of the two chromosomes carries a modifier that either suppresses (Fas2^G0336) or enhances (Fas2^EB112) phenotypic severity. We find not only the latter to be the case, but identify the enhancing mutation asNrg¹⁴, also a classic null allele.