An Axon-Pathfinding Mechanism Preserves Epithelial Tissue Integrity

Epithelial tissues form the boundaries of organs, where they perform a range of functions, including secretion, absorption, and protection. These tissues are commonly composed of discrete cell layers-sheets of cells that are one-cell thick. In multiple systems examined, epithelial cells round up and move in the apical direction before dividing, likely in response to neighbor-cell crowding [1-6]. Because of this movement, daughter cells may be born displaced from the tissue layer. Reintegration of these displaced cells supports tissue growth and maintains tissue architecture [4]. Two conserved IgCAMs (immunoglobulin superfamily cell adhesion molecules), neuroglian (Nrg) and fasciclin 2 (Fas2), participate in cell reintegration in the Drosophila follicular epithelium [4]. Like their vertebrate orthologs L1CAM and NCAM1/2, respectively, Nrg and Fas2 are cell adhesion molecules primarily studied in the context of nervous system development [7-10]. Consistent with this, we identify another neural IgCAM, Fasciclin 3 (Fas3), as a reintegration factor. Nrg, Fas2, and Fas3 are components of the insect septate junction, the functional equivalent of the vertebrate tight junction, but proliferating follicle cells do not have mature septate junctions, and we find that the septate junction protein neurexin IV does not participate in reintegration [11, 12]. Here, we show that epithelial reintegration works in the same way as IgCAM-mediated axon growth and pathfinding; it relies not only on extracellular adhesion but also mechanical coupling between IgCAMs and the lateral spectrin-based membrane skeleton. Our work indicates that reintegration is mediated by a distinct epithelial adhesion assembly that is compositionally and functionally equivalent to junctions made between axons.