Cochlear neurosensory specification and competence: you gata have Gata

Early prosensory specification to develop sensory competence in the otic epithelium is disrupted by mutations of Eya1, Pax2, Sox2, Jag1, and others. Mutations in these genes apparently disrupt competence and may affect Atoh1 upregulation, a gene known to be necessary for hair cell differentiation within the ear. How these genes interact with each other and other factors within the genetic network of the ear to refine and restrict sensory specification and impart competence to the developing organ of Corti is not known. These genes may also interact with other factors to provide the context to allow prosensory cells, after cell cycle exit, to appropriately respond to Atoh1 expression and differentiate as hair cells. Gata3 is expressed throughout the early otic placode. As ear development continues, Gata3 is restricted to all prosensory areas except that of the saccule. In addition, it is expressed in a subset of delaminating neuroblasts, including the spiral ganglion neuronblasts. Gata3 continues to be highly expressed in the cochlear sensory epithelia as cells differentiate, and is expressed in all cells of the organ of Corti through adult. Despite Gata3’s highly prevalent expression in the inner ear very few studies have assessed the role it plays during otic development. Only two studies have assessed inner ear development in the absence of Gata3, and only up to embryonic day (e)11.5 when absence of Gata3 results in lethality. Investigating the role of Gata3 in cochlear neurosensory specification utilizing a mouse Gata3 knockout model and a combination of a conditionally deleted Gata3 line combined with two cre driver lines (Foxg1cre and Pax2cre) circumvents early embryonic lethality. I have shown that Gata3 is absolutely necessary for all cochlear neurosensory development including hair cells.