Null Allele Mystery Solved with CSI-worthy Genetics

A Drosophila egg chamber where the protein Neuroglian (black on white) is not detected by antibody staining in enhancer of Fas2 mutant clones (marked by the absence of magenta in the top image).

The cell-cell adhesion molecule Fasciclin II (Fas2) has long been studied for its evolutionarily-conserved role in the development of the nervous system in animals. It is also expressed in the epithelial tissues where together with a similar protein, Neuroglian (Nrg), it helps to reintegrate misplaced cells born out of the tissue plane. Together, Nrg and Fas2 therefore help to prevent epithelial disorganization that is a hallmark of cancer.  In a new study published in G3, the Bergstralh-Finegan Lab tackled a genetic mystery whereby fruit flies with different null alleles (versions of genes that lead to a loss of function) of Fas2 exhibit dramatically different effects on tissue organization.

“We discovered that some flies that were reported to only carry a Fas2 null allele possessed a second genetic lesion that we called ‘Enhancer of Fas2’. This article details our work in identifying this lesion, which turned out to be an inversion causing a loss of Nrg,” explained Dr. Tara Finegan. “Fruit flies are an important model system in the study of both nervous system and epithelial tissue development. Therefore, this work is significant for fruit fly research community because it identifies why previously published research studying Fas2 is contradictory and helps to further dissect the genetic relationship between Fas2 and Nrg, two genes from the same family that have similar, but not identical functions.

Citation: Finegan TM, Cammarota C, Mendoza Andrade O, Garoutte AM, Bergstralh DT. Fas2EB112: A Tale of Two Chromosomes. G3. 2024 Mar 6:jkae047: