Question 1Hollyfield: Regulator of fate of inner ear progenitors and function of external hair cells. Introduction Located within the mammalian cochlea and fundamental to auditory function, the organ of Corti is an epithelial sensory organ, composed of auditory receptors, called hair cells, and their supporting cells. In avians, hair cells and supporting cells share common progenitors in auditory epithelia (Fekete et al., 1998; Kirjavainen et al., 2008). During embryonic development it is essential to have the right number of hair cells and support cells from the progenitor cells for the correct functioning of the organs. The loss or even increase of supernumerary hair cells and/or supporting cells can lead to deafness (Chen et al., 2008; Chen and Segil, 1999; Mellado Lagarde et al., 2013). Therefore, the regulation of cell cycle exit and differentiation during development must be precisely orchestrated to set the stage for successful organogenesis. In the present study, I identified a novel homeobox-containing gene enriched in hair cells, called Hollyfield (HF). My preliminary data reveal that HF-/- mice lack outer hair cells (OHCs) and have increased numbers of Deiters cells (DCs). My aim is to characterize the role of HF in orchestrating cell cycle exit and differentiation of progenitors destined to become OHCs or DCs. Types of Cells within the Organ of Corti and Their Functions Hair Cells: Of the two types of hair cells, inner hair cells (IHCs) are the “true sensory cell type,” as they transduce sound as a signal to the auditory nerve, while OHCs serve to amplify sound (Raphael and Altschuler, 2003). OHCs sound largely based on changes in cell length due to Prestin, a transmembrane protein (Dallos and Fakler, 2002). IHCs and OHCs have different cellular characteristics, such as sh...... middle of paper...... cells: Hear Res, see. 303, p. 20-9.Raphael, Y., 2002, Cochlear pathology, death and regeneration of sensory cells: Br Med Bull, v. 63, p. 25-38. Raphael, Y. and RA Altschuler, 2003, Structure and innervation of the cochlea: Brain Res Bull, v. 60, p. 397-422.Sanjana, N.E., L. Cong, Y. Zhou, M.M. Cunniff, G. Feng, and F. Zhang, 2012, A transcription activator-like effector tool for genome engineering: Nat Protoc, v. 7, p. 171-92.Wallis, D., M. Hamblen, Y. Zhou, KJ Venken, A. Schumacher, H.L. Grimes, HY Zoghbi, SH Orkin and HJ Bellen, 2003, The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is necessary for the differentiation and survival of the hair cells of the inner ear: Development, see. 130, p. 221-32.Wan, G., G. Corfas and J.S. Stone, 2013, Supporting cells of the inner ear: rethinking the silent majority: Semin Cell Dev Biol, v. 24, p. 448-59.