When whorls collide: the development of hair patterns in frizzled 6 mutant mice

Abstract

SUMMARYSurface appendages such as bristles, feathers and hairs exhibit both long-and short-range order. In the frizzled 6 null (Fz6 -/-) mouse the orientations of the earliest born hair follicles are uncorrelated, but over time the follicles reorient to create patterns that are characterized by a high degree of local order. By quantifying follicle orientations over time, in both living and fixed tissues, we define the time course of local hair follicle refinement and the resulting evolution of a montage of competing patterns in Fz6 -/-skin. We observe an apparently local process that within one week can organize a field of many tens of thousands of follicles, generating long-range order that extends over distances of more than one centimeter. Physical systems that undergo an analogous ordering of vector components suggest potential mechanisms that might apply to the patterning of hair follicles and related biological structures.

Responses of hair follicle–associated structures to loss of planar cell polarity signaling

“…3 P-T). As described by Wang et al (19) and seen in Fig. 3Q (arrowheads), follicles close to the center of a whorl are often bent, suggesting that in this region the local alignment mechanism drives a more extensive reorientation.…”

“…3 F-J, is populated by follicles oriented from anterior to posterior. Although the follicle orientations at this time point closely resemble those of the WT sample, the Fz6 −/− ;ridge/ridge follicles have arrived at these orientations by a more circuitous route because their orientations were highly variable 3 wk earlier (18,19). As seen in Fig.…”

“…3 A-E). The regular arrangement of follicle insertion points at all stages of development suggests that these points are fixed (19). If, in Fz6 −/− skin, the sites of APM attachment at the epidermis were fixed at the same locations as in WT skin, then the APMs would track the reorienting follicles as diagrammed in model A of Fig.…”

“…First defined in Drosophila, PCP signaling is mediated by a core set of approximately six genes that form asymmetric cell surface complexes and convey vectorial information from cell to cell within an epithelium (14). In mice, loss-of-function mutations in Frizzled (Fz)6 or Celsr1, or the semidominant Loop-tail gain-of-function mutation in Vangl2-all homologs of core PCP genes in Drosophila-lead to aberrant hair follicle orientations (15)(16)(17)(18)(19). In Fz6 −/− mice, where this phenomenon has been most extensively studied, follicles on the back initially exhibit orientations that appear approximately random.…”

“…In Fz6 −/− mice, where this phenomenon has been most extensively studied, follicles on the back initially exhibit orientations that appear approximately random. During the first postnatal week, the follicles reorient within the dermis to generate novel hair patterns, including tufts (cow-licks) and whorls (18,19). Pattern formation appears to reflect the actions of a developmental program that aligns neighboring follicles, thereby creating a patchwork of small-scale patterns that compete as each pattern enlarges and becomes more organized.…”