A genomic region encompassing a newly identified exon provides enhancing activity sufficient for normal myo7aa expression in zebrafish sensory hair cells. Issue 9 (19th January 2015)

• Record Type: Journal Article
• Authors: Ernest, Sylvain; Rosa, Frédéric M.
• Is Part Of: Developmental neurobiology. Volume 75:Issue 9(2015:Sep.)
• Page Start: 961
• Page End: 983
• Publication Date: 2015-01-19
• Subjects: Neurobiology -- Periodicals; Neurobiology; Neurobiologie -- Périodiques; Neurobiology; Periodicals; Periodicals; 573.838
• DOI: 10.1002/dneu.22263
• Languages: English
• ISSNs: 1932-8451

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>MYO7A is an unconventional myosin involved in the structural organization of hair bundles at the apex of sensory hair cells (SHCs) where it serves mechanotransduction in the process of hearing and balance. Mutations of MYO7A are responsible for abnormal shaping of hair bundles, resulting in human deafness and murine deafness/circling behavior. Myo7aa, expressed in SHCs of the inner ear and lateral line of zebrafish, causes <italic>circling</italic> behavior and abnormal hair cell function when deficient in <italic>mariner</italic> mutant. This work identifies a new hair cell‐specific enhancer, highly conserved between species, located within Intron 2–3 of zebrafish myosin 7a (<italic>myo7aa</italic>) gene. This enhancer is contained within a 761‐bp DNA fragment that encompasses a newly identified Exon of <italic>myo7aa</italic> and whose activity does not depend on orientation. Compensation of <italic>mariner</italic> mutation by expression of mCherry‐Myo7aa fusion protein under the control of this 761‐bp DNA fragment results in recovery of balance, normal hair bundle shape and restored hair cell function. Two smaller adjacent fragments (344‐bp and 431‐bp), extracted from the 761‐bp fragment, both show hair cell‐specific enhancing activity, with apparently reduced intensity and coverage. These data should help understand the role of Myo7aa in sensory hair cell differentiation and function. They provide tools to decipher how <italic>myo7aa</italic> gene is expressed and regulated in SHCs by allowing the identification of potential transcription factors involved in this process. The discovered enhancer could represent a new target for the identification of deafness‐causing mutations affecting human <italic>MYO7A</italic>. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 961–983, 2015</p> </abstract>