A novel, PCP-dependent tissue organising principle coordinating morphogenesis between embryonic skin epidermal layers

Planar cell polarity (PCP) provides cells and tissues with a sense of direction in relation to the principal body axes of the embryo. In the developing mouse skin, PCP coordinates cell behaviours within the plane of the epidermal basal monolayer. In this report, evidence is presented for a novel, three-dimensional PCP protein-dependent tissue organising principle(s) operating within the mouse embryonic epidermis which coordinates cell long axis orientation across multiple epidermal layers. Here, the core-PCP protein, Frizzled-6 (Fz6), is found within different layers of developing trunk epidermis. Analysis of fz6 mouse mutant skin suggests Fz6 signalling contributes to several aspects of the novel tissue organising principle. Firstly, the robust coordination of epidermal cell long axis orientation between epidermal layers. Secondly, the timing of the switch in epidermal cell long axis orientation between orthogonal principal body axes, circumferential and longitudinal. Finally, the establishment of robust mirror symmetry of epidermal cell long axis orientation between each mouse embryo mid-flank, when viewed across the ventral midline. Local cell arrays/cell rosette-type arrangements within adjacent epidermal layers are implicated in the underlying mechanism coordinating epidermal cell long axis orientation. A previously unreported morphogenetic event within the superficial layers of the nascent epidermis may also rely on three-dimensional tissue polarity processes.