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

Hao Chang, Hugh Cahill, Philip M. Smallwood, Yanshu Wang, Jeremy Nathans

Research output: Contribution to journalArticle

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-/-;Astn2ex5del/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.

Original languageEnglish (US)
Article numbere1005532
JournalPLoS Genetics
Volume11
Issue number9
DOIs
StatePublished - 2015

Fingerprint

hair follicles
modifiers (genes)
Hair Follicle
hair
Hair
hairs
Cell Polarity
exons
Exons
mice
Phenotype
phenotype
postnatal development
setae (animal)
back (body region)
Invertebrates
membrane proteins
Vertebrates
Membrane Proteins
invertebrates

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Identification of Astrotactin2 as a Genetic Modifier That Regulates the Global Orientation of Mammalian Hair Follicles. / Chang, Hao; Cahill, Hugh; Smallwood, Philip M.; Wang, Yanshu; Nathans, Jeremy.

In: PLoS Genetics, Vol. 11, No. 9, e1005532, 2015.

Research output: Contribution to journalArticle

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