Hair cell fate decisions in cochlear development and regeneration

The discovery of avian cochlear hair cell regeneration in the late 1980s and the concurrent development of new techniques in molecular and developmental biology generated a renewed interest in understanding the genetic mechanisms that regulate hair cell development in the embryonic avian and mammalian cochlea and regeneration in the mature avian cochlea. Research from many labs has demonstrated that the development of the inner ear utilizes a complex series of genetic signals and pathways to generate the endorgans, specify cell identities, and establish innervation patterns found in the inner ear. Recent studies have shown that the Notch signaling pathway, the Atoh1/Hes signaling cascade, the stem cell marker Sox2, and some of the unconventional myosin motor proteins are utilized to regulate distinct steps in inner ear development. While many of the individual genes involved in these pathways have been identified from studies of mutant and knockout mouse cochleae, the interplay of all these signals into a single systemic program that directs this process needs to be explored. We need to know not only what genes are involved, but understand how their gene products interact with one another in a structural and temporal framework to guide hair cell and supporting cell differentiation and maturation. (C) 2010 Elsevier B.V. All rights reserved.