COLLAZO, A.*; BRICAUD, O.; KIL, S.-H.; House Ear Institute: Single cell lineage analyses in the developing inner ear: Cellular and molecular contexts

The inner ear and its ganglion are derived from an ectodermal thickening called the otic placode. The placode invaginates to form an otic vesicle or otocyst, a seemingly homogeneous sphere of epithelium, which becomes subdivided into sensory, nonsensory and neurogenic regions. The nonsensory epithelium, in particular, grows extensively and becomes subdivided into distinct but connected chambers, which house the sensory organs. The sensory organs consist of two cell types: hair cells, the highly specialized postmitotic mechanosensory cells, and the surrounding support cells. The placode also contributes to neurons that will form the statoacoustic or VIIIth cranial ganglia. Although the morphology and function of the sensory organs and VIIIth ganglia are well characterized, their origins and lineage relationships are virtually unknown. Single cell lineage analyses in vivo provide the best means to address the developmental potential of a cell and also provide a higher resolution fate map of the inner ear. Single cell lineage analyses in the frog, Xenopus laevis, are consistent with the surprising degree of cell mixing reported in the most recent inner ear fate map done in this species. This contrasts with the relative restriction seen in chick lineage studies. Single cell lineage analyses in zebrafish will help in addressing the lineage relationships between hair cells and statoacoustic neurons. Recent molecular studies using the homeodomain containing transcription factor Six1, reveal it to be the only gene known to differentially affect these two cell types. Understanding the lineage relationships between these cell types is crucial for determining when during inner ear development Six1 is acting. Together these single cell lineage analyses in frog and fish can address issues of cell mixing and provide an assay for gene function in the developing inner ear.