Neural precursor cells of the central nervous system undergo successive temporal waves of terminal division, each of which is soon followed by the onset of cell differentiation. The organ of Corti in the mammalian cochlea develops differently, such that precursors at the apex are the first to exit from the cell cycle but the last to begin differentiating as mechanosensory hair cells. Using a tissuespecific knockout approach in mice, we show that this unique temporal pattern of sensory cell development requires that the adjacent auditory (spiral) ganglion serve as a source of the signaling molecule Sonic hedgehog (Shh). In the absence of this signaling, the cochlear duct is shortened, sensory hair cell precursors exit from the cell cycle prematurely, and hair cell differentiation closely follows cell cycle exit in a similar apical-to-basal direction. The dynamic relationship between the restriction of Shh expression in the developing spiral ganglion and its proximity to regions of the growing cochlear duct dictates the timing of terminal mitosis of hair cell precursors and their subsequent differentiation.morphogenesis | Atoh1 | tonotopy T he mammalian cochlea, a coiled sensory end organ of hearing, contains a specialized mechanosensory epithelium (organ of Corti) consisting of hair cells (HCs) and nonsensory supporting cells. Sound frequency discrimination in mammals begins in the cochlea with a frequency-place code, such that specific frequencies elicit maximal responses of the organ of Corti at different points along its longitudinal (basal-apical) axis, a phenomenon known as tonotopy. Many structural and molecular features of the mature organ of Corti that vary along the longitudinal (tonotopic) axis, including stiffness of the basilar membrane and size and shape of the sensory HCs and their associated stereocilia (1, 2), have been implicated as contributing factors in frequency discrimination. The developmental bases of tonotopy remain obscure, however (3).A possible developmental influence on tonotopy is the wellcharacterized dynamic of apical (low-frequency sensing) precursors exiting early from the cell cycle, evident at embryonic day (E) 12.5 in mice, followed by a wave-like spread of terminal mitosis toward the base (high-frequency sensing), with cells completing cell cycle exit (CCE) by E14.5 (Fig. 1A) (4, 5). In contrast, early markers of HC differentiation, such as atonal homolog 1 (Atoh1), first appear at the midbase at E13.5 and spread bidirectionally along the developing organ of Corti (Fig. 1A) (6). Consequently, apically located HC precursors remain in a postmitotic, undifferentiated state for a longer period than their more basal counterparts. This unusual pattern of cellular regulation is in stark contrast to the neural precursors in the cortex and retina, in which each neuronal subtype has a specific timing of terminal mitosis, followed closely by its differentiation (7,8).Gradients of secreted molecules are important for patterning and cell fate specification during embryogenesis. Although t...

Adults with all levels of hearing loss have faced financial and accessibility constraints in obtaining prescription hearing aids. To increase access to hearing aids, the Food and Drug Administration (FDA) has created a new designation of over-the-counter (OTC) hearing aids for adults with perceived mild to moderate hearing loss. The goal of this article is to describe the incorporation of OTC hearing aid users into established audiology services. A proposed workflow was created by otolaryngologists and audiologists at Johns Hopkins University School of Medicine and is being implemented at outpatient audiology offices. We used published criteria for appropriate OTC hearing aid usage and disqualifying criteria hearing specialists should be aware of. The proposed workflow describes the multiple entry points for OTC hearing aid users seeking access to care and appropriate objectives for these visits. The new FDA ruling has increased the accessibility of hearing assistance devices; however, the varying degrees of retailer support systems could lead to improper fitting and other technical problems for some patients trialing new hearing aids. Our proposed workflow aims to describe the incorporation of established hearing assistance services with the new OTC hearing aid market.