Abstract

Sensory hair cells are coordinately oriented within each inner ear sensory organ to exhibit a particular form of planar cell polarity (PCP) necessary for mechanotransduction. However, the developmental events associated with establishing PCP in the vestibule are unclear, hindering data interpretation and employment of the vestibule for PCP studies. Herein, we investigated PCP of the mouse vestibular organs. We further characterised cell cycle exit, cell differentiation, and PCP establishment in the utricle. We found that hair cells formed first in the striolar and medial extrastriolar (MES) regions of the utricle at embryonic day 11.5 (E11.5), while cells in the lateral extrastriolar region (LES) mostly formed at E13.5. Cell differentiation was initiated in the striolar region, which expanded first toward the MES, then to the LES by E15.5. The polarity of hair cells was established at birth along a putative line of polarity reversal (LPR), lateral to the striolar region. Core PCP protein Vangl2 emerged in the cell boundaries since E11.5, while cell intrinsic polarity protein Gαi3 appeared at E12.5, then polarized to the bare zone of individual hair cell at E13.5. These findings provide a blueprint of the developmental events associated with establishing PCP in the utricle.

Highlights

  • Polarity among neighbouring cells using cell-autonomous and non-cell-autonomous mechanisms[12,13]

  • The utricle and saccule can be divided into three regions: the central striola, the peripheral extrastriola composed of the medial extrastriola (MES), and the lateral extrastriola (LES)

  • Hair cells of opposing directions within otolithic maculae are separated into two domains; membrane hyperpolarisation in one group of macular hair cells and depolarisation in the other group will be evoked by head tilt or an arbitrary linear acceleration

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Summary

Introduction

Polarity among neighbouring cells using cell-autonomous and non-cell-autonomous mechanisms[12,13]. Afterwards, the primary cilium, known as the kinocilium for sensory hair cells, begins to migrate toward the lateral side of the apical surface and is positioned asymmetrically. In the cochlea, this process results in the formation of a staircased and V-shaped stereocilia bundle with the tallest stereocilia near the kinocilium. A single primary cilium is present from the centre of the apical surface and is surrounded by elongated microvilli, which later become stereocilia This primary cilium elongates to form the kinocilium and appears to be relocated to one side of the apical surface of the hair cells, providing the first evidence of intrinsic cellular polarity of individual hair cells[28]. The information presented in the current study is essential for data interpretation of developmental regulations, including PCP regulations, in the utricle

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