Targeting the melanocytes of the inner ear: A comparison of different CreER lines

The inner ear is responsible for hearing and balance. During development, the inner ear undergoes extensive morphogenesis to create a coil shaped cochlea and three semicircular canals from an original flat otic placode. During this morphogenesis, neural crest cells migrate into the inner ear in formation to become either glial cells or melanocytes. The glial cells are located in the cochleo-vestibular ganglion and the melanocytes reside in the stria vascularis in the cochlea and dark cells zone in the vestibule. The stria vascularis pumps potassium ions into the scala media, generating a positive endocochlear potential which is crucial to the mechanosensory cells for auditory signal transduction. Any defect in strial cells leads to the dysregulation of ionic composition of the endolymph, ultimately resulting in deafness. Despite this, we still do not know exactly how the stria vascularis develops and functions. To date, there is an absence of Cre driver mouse lines that effectively facilitate the study of individual cell development and functions within the stria vascularis, limiting our ability to understand strial deafness. Furthermore, the use of CreER transgenic mice lines introduces the possibility of poor recombination and non-specific expression. Therefore, it is necessary to establish a mouse line targeting each cell type within the stria vascularis. The present study aims to determine the most appropriate CreER transgenic line targeting the melanocytes of the inner ear by comparing three CreER mouse lines related to melanocyte development: Pax3, Dct, and Tyr. The CreER mice were crossed with tdTomato reporter mice and induced with tamoxifen at three time points E11.5, P0, and P28 to study the spatiotemporal recombination in the inner ear. We quantify the recombination efficiency in the intermediate cells at each time point and identify important variations in both efficiency and specificity for the three lines. This study focusing on cochlear and vestibular melanocytes provides a much-needed tool to study melanocyte development and function in the inner ear with spatiotemporal control.