The Dachsous/Fat/Four-jointed pathway implements axial long-range cell orientation

Abstract

Despite a cumulative body of knowledge describing short-range cell interactions in morphogenetic processes, relatively little is known on the mechanism involved in the long-range spatial and temporal coordination of cells to build functional and structurally organized tissues. In particular, the attainment of a functionally optimized epithelia must require directional cues to instruct cell movements and cell orientations throughout the tissue field. In Drosophila, the adult epidermis of the abdominal segments is created de novo by the replacement of obsolete larval epidermal cells (LECs) by histoblasts (imaginal founder cells). As these proliferate, expand and fuse, they uniformly organize orienting on the surface along the antero-posterior axis. We found that the coordinated, axially oriented changes in shape of histoblasts respond to a dynamic, yet stereotyped redesign of the epithelial field mediated by the Dachsous/Fat/Four-jointed (Ds/Ft/Fj) pathway. The establishment and refinement of the expression gradients of the atypical cadherins Ds and Ft result in their axial polarization across cell interfaces and differential adhesiveness. We suggest that the role of Ds/Ft/Fj in long-range axially oriented planar cell alignment is a general function and that the regulation of the expression of its components would be crucial in the achievement of tissue uniformity in many other morphogenetic models or during tissue repair.