Document Detail

Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity.
MedLine Citation:
PMID:  22949620     Owner:  NLM     Status:  MEDLINE    
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.
Gary Struhl; José Casal; Peter A Lawrence
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  139     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-05     Completed Date:  2012-11-20     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  3665-74     Citation Subset:  IM    
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MeSH Terms
Animals, Genetically Modified
Body Patterning / genetics*
Cadherins / genetics,  metabolism,  physiology
Cell Polarity / genetics*,  physiology
Drosophila / embryology*,  genetics,  metabolism
Drosophila Proteins / genetics,  metabolism,  physiology*
Embryo, Nonmammalian
Frizzled Receptors / genetics,  metabolism,  physiology*
Gene Expression Regulation, Developmental / physiology*
Membrane Proteins / genetics,  metabolism,  physiology
Models, Biological
Pleura / embryology,  metabolism
Signal Transduction / genetics
Tissue Distribution / genetics
Grant Support
096645//Wellcome Trust; WT086986MA//Wellcome Trust; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Cadherins; 0/Drosophila Proteins; 0/Frizzled Receptors; 0/Membrane Proteins; 0/Vang protein, Drosophila; 0/fz protein, Drosophila; 0/stan protein, Drosophila

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