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bioRxiv · 10.1101/2024.01.03.574100

Fas2: A Tale of Two Chromosomes

Finegan, T. M.·Cammarota, C.·Mendoza Andrade, O.·Garoutte, A. M.·Bergstralh, D. T.
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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.

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Finegan, T. M., Cammarota, C., Mendoza Andrade, O., Garoutte, A. M., Bergstralh, D. T.. 2024-01-04. Fas2: A Tale of Two Chromosomes. https://doi.org/10.1101/2024.01.03.574100

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