# Fas2EB112: a tale of two chromosomes

## TL;DR

This paper solves a genetic mystery about why two Fas2 mutations in fruit flies cause different effects by identifying a modifier mutation in the nrg gene.

## Contribution

The study identifies Nrg14 as the modifier mutation responsible for enhancing the severity of the Fas2EB112 mutation.

## Key findings

- The Fas2EB112 mutation's severe phenotype is enhanced by the Nrg14 mutation.
- The Fas2G0336 mutation shows a mild phenotype due to suppression by a modifier.
- Nrg14 is a classic null allele of the nrg gene, which encodes a cell-cell adhesion molecule.

## Abstract

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.

The cell-cell adhesion molecule Fasciclin II (Fas2) guides nervous system development and acts to preserve epithelial tissue architecture. Here, Finegan et al. solve the genetic mystery of why two different mutations in the fas2 gene in fruit flies cause dramatically different effects. They identify a modifier mutation carried by one of the chromosomes used to study fas2 that disrupts neuroglian (nrg)—a gene that encodes a cell-cell adhesion molecule in the same family as Fas2.