The role of Zic genes in inner ear development in the mouse: Exploring mutant mouse phenotypes. Issue 11 (16th September 2014)

• Record Type: Journal Article
• Authors: Chervenak, Andrew P.; Bank, Lisa M.; Thomsen, Nicole; Glanville‐Jones, Hannah C.; Jonathan, Skibo; Millen, Kathleen J.; Arkell, Ruth M.; Barald, Kate F.
• Is Part Of: Developmental dynamics. Volume 243:Issue 11(2014:Nov.)
• Page Start: 1487
• Page End: 1498
• Publication Date: 2014-09-16
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24186
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <underline>Background:</underline> Murine <italic>Zic</italic> genes (<italic>Zic1–5</italic>) are expressed in the dorsal hindbrain and in periotic mesenchyme (POM) adjacent to the developing inner ear. <italic>Zic</italic> genes are involved in developmental signaling pathways in many organ systems, including the ear, although their exact roles haven't been fully elucidated. This report examines the role of <italic>Zic1</italic>, <italic>Zic2</italic>, and <italic>Zic4</italic> during inner ear development in mouse mutants in which these <italic>Zic</italic> genes are affected. <underline>Results:</underline><italic>Zic1</italic>/<italic>Zic4</italic> double mutants don't exhibit any apparent defects in inner ear morphology. By contrast, inner ears from <italic>Zic2<sup>kd/kd</sup></italic> and <italic>Zic2<sup>Ku/Ku</sup></italic> mutants have severe but variable morphological defects in endolymphatic duct/sac and semicircular canal formation and in cochlear extension in the inner ear. Analysis of otocyst patterning in the <italic>Zic2<sup>Ku/Ku</sup></italic> mutants by in situ hybridization showed changes in the expression patterns of <italic>Gbx2</italic> and <italic>Pax2</italic>. <underline>Conclusions:</underline> The experiments provide the first genetic evidence that the <italic>Zic</italic> genes are required for morphogenesis of the inner ear. <italic>Zic2</italic> loss‐of‐function doesn't prevent initial otocyst patterning but leads to molecular abnormalities concomitant with morphogenesis of the endolymphatic duct. Functional hearing deficits often accompany inner ear dysmorphologies, making <italic>Zic2</italic> a novel candidate gene for ongoing efforts to identify the genetic basis of human hearing loss. <italic>Developmental Dynamics 243:1487–1498, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </abstract>