CONSERVED ROLE OF EMX2 IN ESTABLISHING POLARITY OF SENSORY HAIR CELLS

Abstract

Sensory hair cells in the inner ear are responsible for relaying information such as sounds and head positions to the brain. Stereocilia, which are specialized microvilli, are arranged in a staircase-pattern with the longest row sitting adjacent to the kinocilium. These two structures together form the stereociliary bundle (hair bundle), which are polarized asymmetrically at the apical surface of the hair cell. Deflection of the stereocilia towards the kinocilium opens the mechanotransduction channels at the tip of the stereocilia, which enables ion influx to depolarize the hair cell and activates action potentials in the postsynaptic neurons. Deflection towards the opposite direction results in hyperpolarization. Thus, the stereociliary bundle polarity defines the directional sensitivity of a given hair cell.

Each sensory hair cell organ displays a specific pattern of stereocilia polarity. In the maculae, which detect linear acceleration in all directions, HCs can be divided into two regions with opposite polarity by a line of polarity reversal (LPR). Similar LPR is also present in the neuromast of the zebrafish lateral line system that detect pressure change of surrounding water.

My results show that the homeodomain transcription factor Emx2 is essential for establishing the LPR. Expression of Emx2 in the maculae and neuromasts determines the stereocilia polarity pattern in a cell-autonomous fashion. Gain- and loss-of-function in the sensory hair cell organs of mouse and zebrafish indicate that the role of Emx2 in polarity reversal is both necessary and sufficient. In addition, my results demonstrated that Emx2 mediates this polarity reversal via one of the heterotrimer G-proteins, Gαi. In summary, my results show that Emx2 has a conserved role in dictating stereociliary bundle polarity.