FIGURE 2.

Asymmetries in Inner ear development. (A) Development of stereocilia and kinocilia asymmetric localization on the apical portion of hair cells. The top row is a side view while the bottom row is a top down view of hair cell kinocilia in red and microvillistereocilia in green. As development progresses, the kinocilium migrates into an off-center position devoid of microvilli. The microvilli trailing the kinocilium grow in length and thickness and eventually develop into stereocilia. As the kinocilium reaches its asymmetric position, the stereocilia have formed their typical staircase arrangement whereas microvilli have disappeared. Differential development generates four general types of hair cells with distinctive stereocilia diameter and distribution. In the organ of Corti, hair cells eventually lose their kinocilia. The side view shows a Type I vestibular hair cell and a cochlear outer hair cell. (B) The distribution of PCP proteins in Drosophila, vestibular hair cells, and cochlear hair cells and resulting orientations of hair bristle/stereocilia (black). In the fly and in vestibular hair cells, Prickle (Prickle 2) and Van Gogh reside on one side of the cell, Frizzled and Disheveled on the other and Flamingo/Celsr1 is distributed on both sides of the cell. In vestibular hair cells, while the distribution of PCP proteins remains constant, stereocilia orient in opposing polarities at the line of polarity reversal. In cochlear hair cells, Frizzled3/6 and Celsr1 are expressed on one side, opposite the stereocilia. Data on mutations in PCP genes in the vertebrate suggest that the loss of individual PCP proteins differentially affects hair cells within an epithelium and hair cells between epithelia. (C) In Prickle1 mutants, there is an overlap of branches of apical afferents (blue arrow) with basal afferents (red arrow), in contrast to the maintenance of tonotopic projections in wild type mice. Based on this phenotype, we hypothesize that for spiral ganglion afferent segregation the diffusible Wnts factors released from the dorsal hindbrain (gray gradient) play a role. Abbreviations: HC, hair cell; IHC, Inner hair cell; OHC, outer hair cell; Vangl1/2, Van Gogh-like 1/2; Lp, Looptail.