title: The spatio-temporal domains of Frizzled6 action in planar polarity control of hair follicle orientation.
abstract: In mammals, hair follicles cover most of the body surface and exhibit precise and stereotyped orientations relative to the body axes. Follicle orientation is controlled by the planar cell polarity (PCP; or, more generally, tissue polarity) system, as determined by the follicle mis-orientation phenotypes observed in mice with PCP gene mutations. The present study uses conditional knockout alleles of the PCP genes Frizzled6 (Fz6), Vangl1, and Vangl2, together with a series of Cre drivers to interrogate the spatio-temporal domains of PCP gene action in the developing mouse epidermis required for follicle orientation. Fz6 is required starting between embryonic day (E)11.5 and E12.5. Eliminating Fz6 in either the anterior or the posterior halves of the embryo or in either the feet or the torso leads to follicle mis-orientation phenotypes that are limited to the territories associated with Fz6 loss, implying either that PCP signaling is required for communicating polarity information on a local but not a global scale, or that there are multiple independent sources of global polarity information. Eliminating Fz6 in most hair follicle cells or in the inter-follicular epidermis at E15.5 suggests that PCP signaling in developing follicles is not required to maintain their orientation. The asymmetric arrangement of Merkel cells around the base of each guard hair follicle dependents on Fz6 expression in the epidermis but not in differentiating Merkel cells. These experiments constrain current models of PCP signaling and the flow of polarity information in mammalian skin.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
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, MD 21205, United States; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
authors.forename: John
authors.initials: J
authors.lastname: Williams
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States. Electronic address: jnathans@jhmi.edu.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000818:Animals; D019521:Body Patterning; D002352:Carrier Proteins / Q000378:metabolism; D016764:Cell Polarity; D004622:Embryo, Mammalian / Q000378:metabolism; D051157:Frizzled Receptors / Q000737:chemistry* / Q000378:metabolism*; D017930:Genes, Reporter; D018859:Hair Follicle / Q000166:cytology* / Q000196:embryology*; D019426:Integrases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018862:Merkel Cells / Q000166:cytology / Q000378:metabolism; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009928:Organ Specificity; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D051157:Frizzled Receptors; C111048:Fzd6 protein, mouse; C431577:Ltap protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C528120:Vangl1 protein, mouse; C045073:Cre recombinase; D019426:Integrases
keywords: Fz6; Merkel cell; Mouse development; Planar cell polarity; Skin; Tissue polarity; Vangl1; Vangl2