Fas2EB112: A Tale of Two Chromosomes

• Published in: G3 : genes - genomes - genetics Vol. 14; no. 5
• Main Authors: Finegan, Tara M, Cammarota, Christian, Mendoza Andrade, Oscar, Garoutte, Audrey M, Bergstralh, Dan T
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 07.05.2024
• Subjects: Investigation; Genetics; Adhesion; Drosophila; Epithelia
• ISSN: 2160-1836; 2160-1836
• 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.