Testin Interacts with Vangl2 Genetically to Regulate Inner Ear Sensory Cell Orientation and the Normal Development of the Female Reproductive Tract in Mice

• Type of Material: Article
• Authors: Dongdong Ren, Emory University; Michael Kelly, Emory University; Sun Myoung Kim, Emory University; Cynthia Grimsley-Myers, Emory University; Fang-Lu Chi, Fudan University; Ping Chen, Emory University
• Language: English
• Date: 2013-12-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/dvdy.24042
• Title of Journal or Parent Work: Developmental Dynamics
• ISSN: 1058-8388
• Volume: 242
• Issue: 12
• Start Page: 1454
• End Page: 1465
• Grant/Funding Information: This research was supported in part by the Neuronal Imaging Core of the Emory Neuroscience NINDS Core Facilities grant P30NS055077.; This study is supported by NIH research grants RO1 DC007423 and DC005213 to P. C., NSFC grant 81028003/H1305 to P. C. and F. C., NSFC grant 81000413/H1305 to D.R., International Cooperation projects- of Shanghai Science and Technology Committee (10410700800) to F.C and P.C., Shanghai Rising-Star Program (A type) 11QA1401100 to D.R., Key Basic Research Project of the Science and Technology Commission of Shanghai Municipality (10JC1402500) to F.C.
• Keywords: LUNG DEVELOPMENT; OUTFLOW TRACT; VERTEBRATE EMBRYOS; hair cells; LOOP-TAIL; NEURAL-TUBE DEFECTS; testin; PLANAR POLARITY; FOCAL ADHESION PROTEIN; Anatomy & Morphology; vangl2; Life Sciences & Biomedicine; planar cell polarity; STRABISMUS/VAN-GOGH; Developmental Biology; TUMOR-SUPPRESSOR; Science & Technology; inner ear; HAIR-CELLS; female reproductive tract
• Research Categories: Biology, Animal Physiology; Biology, Genetics

Abstract

Background: Planar cell polarity (PCP) signaling regulates the coordinated polarization of cells and is required for the normal development and function of many tissues. Previous studies have identified conserved PCP genes, such as Van Gogh-like 2 (Vangl2) and Prickle (Pk), in the regulation of coordinated orientation of inner ear hair cells and female reproductive tract development. Testin shares a PET-LIM homology with Pk. It is not clear whether Testin acts in PCP processes in mammals. Results: We identified Testin as a Vangl2-interacting protein through a 2-hybrid screen with a cochlea cDNA library. Testin is enriched to cell-cell boundaries in the presence of Vangl2 in cultured cells. Genetic inactivation of Testin leads to abnormal hair cell orientation in the vestibule and cellular patterning defects in the cochlea. In addition, Testin genetically interacts with Vangl2 to regulate hair cell orientation in the cochlea and the opening of the vaginal tract. Conclusions: Our findings suggested Testin as a gene involved in coordinated hair cell orientation in the inner ear and in female reproductive tract development. Furthermore, its genetic interaction with Vangl2 implicated it as a potential molecular link, responsible for mediating the role of Vangl2-containing membranous PCP complexes in directing morphologic polarization. Developmental Dynamics 242:1454-1465, 2013.