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Disruption of planar cell polarity signaling results in congenital heart defects and cardiomyopathy attributable to early cardiomyocyte disorganization

Lookup NU author(s): Dr Helen PhillipsORCiD, Dr Hong Jun Rhee, Dr Victoria Hildreth, Dr Jonathan Peat, Professor Bob Anderson, Dr Bill Chaudhry, Professor Deborah HendersonORCiD


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The Drosophila scribble gene regulates apical-basal polarity and is implicated in control of cellular architecture and cell growth control. Mutations in mammalian Scrib (circletail; Crc mutant) also result in abnormalities suggestive of roles in planar cell polarity regulation. We show that Crc mutants develop heart malformations and cardiomyopathy attributable to abnormalities in cardiomyocyte organization within the early heart tube. N-Cadherin is lost from the cardiomyocyte cell membrane and cell-cell adhesion is disrupted. This results in abnormalities in heart looping and formation of both the trabeculae and compact myocardium, which ultimately results in cardiac misalignment defects and ventricular noncompaction. Thus, these late abnormalities arise from defects occurring at the earliest stages of heart development. Mislocalization of Vangl2 in Crc/Crc cardiomyocytes suggests Scrib is acting in the planar cell polarity pathway in this tissue. Moreover, double heterozygosity for mutations in both Scrib and Vangl2 can cause cardiac defects similar to those found in homozygous mutants for each gene but without other major defects. We propose that heterozygosity for mutations in different genes in the planar cell polarity pathway may be an important mechanism for congenital heart defects and cardiomyopathy in humans. © 2007 American Heart Association, Inc.

Publication metadata

Author(s): Peat JD; Henderson DJ; Hildreth V; Phillips HM; Anderson RH; Chaudhry B; Rhee HJ; Murdoch JN; Copp AJ

Publication type: Article

Publication status: Published

Journal: Circulation Research

Year: 2007

Volume: 101

Issue: 2

Pages: 137-145

ISSN (print): 0009-7330

ISSN (electronic): 1524-4571

Publisher: Lippincott Williams & Wilkins


DOI: 10.1161/CIRCRESAHA.106.142406

PubMed id: 17556662


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Funder referenceFunder name
068883Wellcome Trust
G120/861Medical Research Council
PG/11/76/29108British Heart Foundation