title: Cohesin controls planar cell polarity by regulating the level of the seven-pass transmembrane cadherin Flamingo.
abstract: Planar cell polarity (PCP) refers to the coordination of global organ axes and individual cell polarity in vertebrate and invertebrate epithelia. Mechanisms of PCP have been best studied in the Drosophila wing, in which each epidermal cell produces a single wing hair at the distal cell edge, and this spatial specification is mediated by redistribution of the core group proteins, including the seven-pass transmembrane cadherin Flamingo/Starry night (Fmi/Stan), to selective plasma membrane domains. Through genetic screening, we found that a mutation of the SMC3 gene caused dramatic misspecification of wing hair positions. SMC3 protein is one subunit of the cohesin complex, which regulates sister chromatid cohesion and also plays a role in transcriptional control of gene expression. In the SMC3 mutant cells, Fmi appeared to be upregulated by a posttranscriptional mechanism(s), and this elevation of Fmi was at least one cause of the PCP defect. In addition to the PCP phenotype, the loss of the cohesin function affected wing morphogenesis at multiple levels: one malformation was loss of the wing margin, and this was most likely a result of downregulation of the homeodomain protein Cut. At the cellular level, apical cell size and hexagonal packing were affected in the mutant wing. Dysfunction of cohesin in humans results in Cornelia de Lange syndrome (CdLS), which is characterized by various developmental abnormalities and mental retardation. Our analysis of cohesin in epithelia may provide new insight into cellular and molecular mechanisms of CdLS.
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Mouri
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Horiuchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Uemura
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D016764:Cell Polarity; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004330:Drosophila / Q000166:cytology* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D015820:Cadherins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000097722:Cohesins; C066381:ct protein, Drosophila; C121420:stan protein, Drosophila; C541514:SMC3 protein, Drosophila