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

PLoS Genet. 2015 Sep 29;11(9):e1005532. doi: 10.1371/journal.pgen.1005532. eCollection 2015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Cell Polarity
  • Frizzled Receptors / genetics*
  • Glycoproteins / genetics*
  • Glycoproteins / physiology
  • Hair Follicle / growth & development*
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Signal Transduction


  • Astn2 protein, mouse
  • Frizzled Receptors
  • Glycoproteins
  • Nerve Tissue Proteins