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University of Rochester

1. Steevens, Aleta R. The Dynamic Role of SOX2 in Mammalian Inner Ear Development.

Degree: PhD, 2020, University of Rochester

Intricate neuroanatomical structures within our inner ears confer humans with the ability to detect sound and balance information with exquisite detail. These abilities are mediated by six sensory organs and the specialized sensory cells that make up these regions: mechanosensory hair cells, supporting cells, and inner ear neurons. Hair cells and supporting cells derive from a common sensory progenitor, and in some cases, all three cell types arise from a common neurosensory progenitor. Generating a better understanding of how sensory cells develop from a progenitor stage will further therapeutic strategies aimed at regenerating damaged sensory areas in hearing and balance disorders, in which cellular deficits are permanent. The transcription factor SOX2 is firmly established to be required for inner ear sensory progenitor formation. Additionally, overexpression studies have suggested that SOX2 may promote the generation of both neuronal and sensory inner ear lineages. However, it is not known when SOX2 is required nor in which cells types. Thus, an outstanding question remains: is SOX2 exclusive to sensory progenitors from the earliest times? In order to determine when and in which cell types SOX2 acts during inner ear development, I used a genetic system in the mouse to fate map early SOX2 expressing progeny and to test the requirements of SOX2 activity during critical inner ear development stages. I discovered several novel and previously unrecognized roles for SOX2 in inner ear development that includes the following: (1) SOX2 is required for inner ear neurogenesis and acts upstream in a cascade of proneural signaling events. (2) SOX2 initially is required for non-sensory development in the cochlea and for vestibular formation. (3) Loss and gain-of-function approaches indicate an early role for SOX2 in promoting inner ear progenitor proliferation. Moreover, I showed that SOX2 does not mark the sensory lineage from the earliest times, but rather sensory specification is a later function of SOX2. Interestingly, short harvest fate mapping experiments captured the dynamics in SOX2 expression and function, as the entire domain of SOX2 inverted within a 48-hour window. Likely this reflects its switch from promoting non-sensory formation and proliferation to sensory development in the cochlea. These studies reveal the dynamic role for SOX2 in inner ear development and outline the parameters in which SOX2 promotes different otic lineages.

Subjects/Keywords: Development; Inner ear; Neurogenesis; Sensory specification; SOX2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Steevens, A. R. (2020). The Dynamic Role of SOX2 in Mammalian Inner Ear Development. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/35509

Chicago Manual of Style (16th Edition):

Steevens, Aleta R. “The Dynamic Role of SOX2 in Mammalian Inner Ear Development.” 2020. Doctoral Dissertation, University of Rochester. Accessed April 09, 2020. http://hdl.handle.net/1802/35509.

MLA Handbook (7th Edition):

Steevens, Aleta R. “The Dynamic Role of SOX2 in Mammalian Inner Ear Development.” 2020. Web. 09 Apr 2020.

Vancouver:

Steevens AR. The Dynamic Role of SOX2 in Mammalian Inner Ear Development. [Internet] [Doctoral dissertation]. University of Rochester; 2020. [cited 2020 Apr 09]. Available from: http://hdl.handle.net/1802/35509.

Council of Science Editors:

Steevens AR. The Dynamic Role of SOX2 in Mammalian Inner Ear Development. [Doctoral Dissertation]. University of Rochester; 2020. Available from: http://hdl.handle.net/1802/35509

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