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- W3201235969 abstract "Intricate neuroanatomical structures within ourinner ears confer humans with the ability to detect sound andbalance information with exquisite detail. These abilities aremediated by six sensory organs and the specialized sensory cellsthat make up these regions: mechanosensory hair cells, supportingcells, and inner ear neurons. Hair cells and supporting cellsderive from a common sensory progenitor, and in some cases, allthree cell types arise from a common neurosensory progenitor.Generating a better understanding of how sensory cells develop froma progenitor stage will further therapeutic strategies aimed atregenerating damaged sensory areas in hearing and balancedisorders, in which cellular deficits are permanent. Thetranscription factor SOX2 is firmly established to be required forinner ear sensory progenitor formation. Additionally,overexpression studies have suggested that SOX2 may promote thegeneration of both neuronal and sensory inner ear lineages.However, it is not known when SOX2 is required nor in which cellstypes. Thus, an outstanding question remains: is SOX2 exclusive tosensory progenitors from the earliest times? In order to determinewhen and in which cell types SOX2 acts during inner eardevelopment, I used a genetic system in the mouse to fate map earlySOX2 expressing progeny and to test the requirements of SOX2activity during critical inner ear development stages. I discoveredseveral novel and previously unrecognized roles for SOX2 in innerear development that includes the following: (1) SOX2 is requiredfor inner ear neurogenesis and acts upstream in a cascade ofproneural signaling events. (2) SOX2 initially is required fornon-sensory development in the cochlea and for vestibularformation. (3) Loss and gain-of-function approaches indicate anearly role for SOX2 in promoting inner ear progenitorproliferation. Moreover, I showed that SOX2 does not mark thesensory lineage from the earliest times, but rather sensoryspecification is a later function of SOX2. Interestingly, shortharvest fate mapping experiments captured the dynamics in SOX2expression and function, as the entire domain of SOX2 invertedwithin a 48-hour window. Likely this reflects its switch frompromoting non-sensory formation and proliferation to sensorydevelopment in the cochlea. These studies reveal the dynamic rolefor SOX2 in inner ear development and outline the parameters inwhich SOX2 promotes different otic lineages." @default.
- W3201235969 created "2021-09-27" @default.
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- W3201235969 date "2020-01-01" @default.
- W3201235969 modified "2023-09-26" @default.
- W3201235969 title "The Dynamic Role of SOX2 in Mammalian Inner EarDevelopment" @default.
- W3201235969 hasPublicationYear "2020" @default.
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