Clonal analysis in chick showed that neurons of the cochleo-vestibular ganglion can be related to utricular epithelial cells ( Satoh and Fekete, 2005), although the lack of genetic tools did not allow precise localization of the original targeted cell. The neurogenic region partially overlaps with the sites in which sensory patches will develop ( Haddon et al., 1998 Andermann et al., 2002 Millimaki et al., 2007 Sapède and Pujades, 2010), raising the question of whether neurons and hair cells arise from a common progenitor cell. In zebrafish, neurogenesis and hair cell specification take place simultaneously ( Haddon and Lewis, 1996).
The molecular basis of neurosensory development has been studied extensively, and it depends on the function of three proneural genes: atoh1 for hair cell formation ( Bermingham et al., 1999 Millimaki et al., 2007), neurog1 for sensory neuron determination ( Ma et al., 1998 Andermann et al., 2002), and neuroD1 for sensory neuron differentiation and survival ( Kim et al., 2001 Jahan et al., 2010a). This requires a tight coordination between morphogenesis and cell fate specification. Thus, to ultimately provide replacement of lost neurosensory cells, it is essential to unveil the mechanisms for determining the fate of these cell types from early progenitors.Īll the cellular components of the inner ear, afferent neurons and both sensory and nonsensory epithelia, arise from the otic placode, a simple ectodermal thickening adjacent to the hindbrain. In mammals, these neurosensory cells have a limited regeneration capacity, and their lifespan is truncated by numerous environmental conditions and a genetic predisposition, leading to an increase of age-dependent progressive hearing loss ( Corwin and Cotanche, 1988 Bermingham-McDonogh and Rubel, 2003). In vertebrates, two key cell types underlie the function of mechanosensory systems: the hair cells that transduce the mechanical stimuli and the sensory afferent neurons that conduct the extracted information to the brainstem. Combined results from single-cell lineage and functional studies on neurog1 and neuroD1 further demonstrate the following: (1) in the anterior region of the ear, neuronal and sensory lineages have already segregated at the onset of proneural gene expression and are committed to a given fate very early (2) in contrast, the posteromedial part of the ear harbors a population of common progenitors giving both neurons and hair cells until late stages and finally (3) neuroD1 is required within this pool of bipotent progenitors to generate the hair cell fate. Expression analysis reveals that proneural genes for hair cells and neurons overlap within the posteromedial otic epithelium. Here, we identified a population of common neurosensory progenitors in the zebrafish inner ear and studied the proneural requirement for cell fate decision within this population.
Although there is little evidence for a clonal relationship between macular hair cells and sensory neurons, the existence of a single progenitor able to give both sensory and neuronal cell types remains an open question.
Various studies have shown that hair cell- and neuron-specifying genes partially overlap in the otic territory, suggesting that mutual interactions among these bHLH factors could direct the generation of the two cell types from a common neurosensory progenitor. However, the molecular mechanisms regulating the generation of the appropriate cell type in the correct place and at the correct time are not completely understood yet. In the inner ear, sensory versus neuronal specification is achieved through few well-defined bHLH transcription factors.
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