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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.

Identification of Astrotactin2 as a Genetic Modifier That Regulates the Global Orientation of Mammalian Hair Follicles