title: Identification of Astrotactin2 as a Genetic Modifier That Regulates the Global Orientation of Mammalian Hair Follicles.
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.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Hao
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Hugh
authors.initials: H
authors.lastname: Cahill
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Smallwood
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D016764:Cell Polarity; D051157:Frizzled Receptors / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics* / Q000502:physiology; D018859:Hair Follicle / Q000254:growth & development*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction
chemical_list: C550779:Astn2 protein, mouse; D051157:Frizzled Receptors; D006023:Glycoproteins; D009419:Nerve Tissue Proteins