title: Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity.
abstract: Many epithelia have a common planar cell polarity (PCP), as exemplified by the consistent orientation of hairs on mammalian skin and insect cuticle. One conserved system of PCP depends on Starry night (Stan, also called Flamingo), an atypical cadherin that forms homodimeric bridges between adjacent cells. Stan acts together with other transmembrane proteins, most notably Frizzled (Fz) and Van Gogh (Vang, also called Strabismus). Here, using an in vivo assay for function, we show that the quintessential core of the Stan system is an asymmetric intercellular bridge between Stan in one cell and Stan acting together with Fz in its neighbour: such bridges are necessary and sufficient to polarise hairs in both cells, even in the absence of Vang. By contrast, Vang cannot polarise cells in the absence of Fz; instead, it appears to help Stan in each cell form effective bridges with Stan plus Fz in its neighbours. Finally, we show that cells containing Stan but lacking both Fz and Vang can be polarised to make hairs that point away from abutting cells that express Fz. We deduce that each cell has a mechanism to estimate and compare the numbers of asymmetric bridges, made between Stan and Stan plus Fz, that link it with its neighbouring cells. We propose that cells normally use this mechanism to read the local slope of tissue-wide gradients of Fz activity, so that all cells come to point in the same direction.
authors.affiliation: Department of Genetics and Development, HHMI, HHSC, College of Physicians and Surgeons, 701 West 168th Street, Room 1116, New York, NY 10032, USA. gs20@columbia.edu
authors.forename: Gary
authors.initials: G
authors.lastname: Struhl
authors.forename: José
authors.initials: J
authors.lastname: Casal
authors.forename: Peter A
authors.initials: PA
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics* / Q000502:physiology; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D010994:Pleura / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014018:Tissue Distribution / Q000235:genetics
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008565:Membrane Proteins; C111638:Vang protein, Drosophila; C058784:fz protein, Drosophila; C121420:stan protein, Drosophila