title: Frizzled Receptors in Development and Disease.
abstract: Frizzled proteins are the principal receptors for the Wnt family of ligands. They mediate canonical Wnt signaling together with Lrp5 and Lrp6 coreceptors. In conjunction with Celsr, Vangl, and a small number of additional membrane and membrane-associated proteins, they also play a central role in tissue polarity/planar cell polarity (PCP) signaling. Targeted mutations in 9 of the 10 mammalian Frizzled genes have revealed their roles in an extraordinarily diverse set of developmental and homeostatic processes, including morphogenetic movements responsible for palate, ventricular septum, ocular furrow, and neural tube closure; survival of thalamic neurons; bone formation; central nervous system (CNS) angiogenesis and blood-brain barrier formation and maintenance; and a wide variety of processes that orient subcellular, cellular, and multicellular structures relative to the body axes. The last group likely reflects the mammalian equivalent of tissue polarity/PCP signaling, as defined in Drosophila, and it includes CNS axon guidance, hair follicle and tongue papilla orientation, and inner ear sensory hair bundle orientation. Frizzled receptors are ubiquitous among multicellular animals and, with other signaling molecules, they very likely evolved to permit the development of the complex tissue architectures that provide multicellular animals with their enormous selective advantage.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Rattner
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address: jnathans@jhmi.edu.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000818:Animals; D016764:Cell Polarity; D004194:Disease; D051157:Frizzled Receptors / Q000378:metabolism*; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051157:Frizzled Receptors
keywords: Angiogenesis; Axon guidance; Blood–brain barrier; Hair follicles; Planar cell polarity; Tissue polarity