Abstract
Planar cell polarity (PCP) signaling controls the global orientation of surface structures, such as hairs and bristles, in both vertebrates and invertebrates. In Frizzled6 -/- (Fz6 -/-) mice, hair follicle orientations on the head and back are nearly random at birth, but reorient during early postnatal development to eventually generate a nearly parallel anterior-to-posterior array. We report the identification of a naturally occurring exon 5 deletion in Astrotactin2 (Astn2) that acts as a recessive genetic modifier of the Fz6 -/- hair patterning phenotype. A genetically engineered Astn2 exon 5 deletion recapitulates the modifier phenotype. In Fz6 -/- ;Astn2 ex5del/del mice, hair orientation on the back is subtly biased from posterior-to-anterior, leading to a 180-degree orientation reversal in mature mice. These experiments suggest that Astn2, an endosomal membrane protein, modulates PCP signaling.
Highlights
In complex multi-cellular organisms, individual surface structures such as hairs, feathers, scales, and bristles typically exhibit a high degree of spatial order
The first clues to the mechanism of hair patterning in mammals came from genetic analyses of proteins that are homologous to a small set of Drosophila proteins that control patterning of bristles and hairs on the insect body surface and wings
Hair follicle orientation is controlled by planar cell polarity (PCP) signaling, as determined by the changes in follicle orientation associated with mutations in the core PCP genes Frizzled6 (Fz6), Celsr1, and Van Gogh-like2 (Vangl2) in mice [1,2,3,4,5]
Summary
In complex multi-cellular organisms, individual surface structures such as hairs, feathers, scales, and bristles typically exhibit a high degree of spatial order. In the absence of Fz6, the initial orientations of hair follicles on the head and back appear to be largely randomized, in contrast to the nearly parallel orientations of follicles on most of the body surface of wild type (WT) mice. During the first postnatal week, hair follicles in WT mice undergo a subtle reorientation, referred to as “refinement”, which minimizes angular differences among neighboring follicles. This process leads to a more precise alignment of follicles with the body axes (on the back) or with local anatomic structures (on the limbs) [2,3]. In Fz6-/- back skin, this process leads initially to a series of large-scale patterns, such as whorls, most of which disappear by postnatal day (P)10-P15 as the field of follicle vectors progressively aligns along an anterior-toposterior direction
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