Regulation of cochlear convergent extension by the vertebrate planar cell polarity pathway is dependent on p120-catenin

• Type of Material: Article
• Authors: Maria F. Chacon-Heszele, Emory University; Dongdong Ren, Emory University; Albert B. Reynolds, Vanderbilt University; Fanglu Chi, Fudan University; Ping Helen Chen, Emory University
• Language: English
• Date: 2012-03-01
• Publisher: Company of Biologists
• Publication Version: Final Published Version
• Copyright Statement: © 2012. Published by The Company of Biologists Ltd
• Final Published Version (URL): http://dev.biologists.org/content/139/5/968
• Title of Journal or Parent Work: Development
• Volume: 139
• Issue: 5
• Start Page: 968
• End Page: 978
• Grant/Funding Information: This study was supported in part by the Neuronal Imaging Core of the Emory Neuroscience National Institute of Neurological Disorders and Stroke (NINDS) Core Facilities grant [P30NS055077].; Natural Science Foundation of China (NSFC) grants [81028003/H1305 to P.C. and F.C., and 81000413/H1305 to D.R.]; This study was supported by National Institutes of Health grants [RO1 DC007423 and DC005213 to P.C.]; Shanghai Rising-Star Program A-type grant [11QA1401100] and the Research Fund for the Doctoral Program of High Education grant [20110071120086] to D.R.
• Keywords: Mouse; Cochlea; Planar cell polarity; Adhesion
• Research Categories: Biology, Cell; Health Sciences, Human Development

Abstract

The vertebrate planar cell polarity (PCP) pathway consists of conserved PCP and ciliary genes. During development, the PCP pathway regulates convergent extension (CE) and uniform orientation of sensory hair cells in the cochlea. It is not clear how these diverse morphogenetic processes are regulated by a common set of PCP genes. Here, we show that cellular contacts and geometry change drastically and that the dynamic expression of N-cadherin and E-cadherin demarcates sharp boundaries during cochlear extension. The conditional knockout of a component of the adherens junctions, p120-catenin, leads to the reduction of E-cadherin and N-cadherin and to characteristic cochlear CE defects but not misorientation of hair cells. The specific CE defects in p120-catenin mutants are in contrast to associated CE and hair cell misorientation defects observed in common PCP gene mutants. Moreover, the loss-of-function of a conserved PCP gene, Vangl2, alters the dynamic distribution of N-cadherin and E-cadherin in the cochlea and causes similar abnormalities in cellular morphology to those found in p120-catenin mutants. Conversely, we found that Pcdh15 interacts genetically with PCP genes to regulate the formation of polar hair bundles, but not CE defects in the cochlea. Together, these results indicate that the vertebrate PCP pathway regulates CE and hair cell polarity independently and that a p120-catenin-dependent mechanism regulates CE of the cochlea.