Fas2[EB112]: A Tale of Two Chromosomes

• Published in: bioRxiv
• Main Authors: Finegan, Tara M, Cammarota, Christian, Oscar Mendoza Andrade, Garoutte, Audrey M, Bergstralh, Dan T
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 04.01.2024
• Subjects: Alleles; Axon guidance; Cell adhesion molecules; Chromosomes; Epithelium; FAS2 protein; Phenotypes; Proteins
• DOI: 10.1101/2024.01.03.574100

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 allele Fas2[EB112] 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[EB112] has been used in at least 37 research articles, and Fas2[G0336] in 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 as Nrg14, also a classic null allele.Competing Interest StatementThe authors have declared no competing interest.