Investigating the formation of spatial and directional patterns in the mammalian epidermis

Abstract

Organs harbor specialized cell types and structures arranged in precise and repeated patterns. Striped and spotted patterns of pigmented cells in the skin, epithelial branches of the lung and kidney, and sensory bristles that decorate insect cuticles are notable examples. Periodically patterned structures such as body hairs and sensory bristles also display directional patterning, known as planar cell polarity (PCP), where each functional unit is polarized and collectively aligned along the tissue plane. Here, using live-imaging combined with genetic, pharmacological, and physical manipulations we investigate the interplay between the spatial and directional systems in the mammalian epidermis that produces a pattern of evenly spaced, planar polarized multicellular structures. We uncover the cellular basis of hair follicle polarization and define the role of PCP in generating asymmetry in this multicellular system. We find that PCP and myosin activity drive counter-rotational cell flows, movements that transform an initially radially symmetric placode into one that is a planar polarized. We then go on to define how a radial pattern within each developing placode is first established, and investigate how the redial pattern contributes to polarized morphogenesis. We find that Wnt specifies and maintains inner cell fate, and through Shh signaling, specifies outer cell fates. While inner cells can rearrange on their own, they require outer cells to compartmentalize their movements and properly pattern them into a counter-rotational cell flow. We end by describing the remarkable plasticity of the mammalian skin to form properly spaced hair follicles despite extreme perturbations to either the epidermis or dermis.