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Role of ISL1 in development of neurosensory cells of inner ear
Vochyánová, Simona ; Pavlínková, Gabriela (advisor) ; Machoň, Ondřej (referee)
To understand the pathophysiology of hearing loss, it is necessary to identify genes responsible for embryonic development of neurosensory cells in the inner ear. The aim of this work is to clarify the role of LIM-homeodomain transcription factor ISL1 in the development of these cells. Using Cre-loxP recombination strategy, we generated a mouse line with time and site- specific deletion of Isl1 gene in NEUROD1-Cre expressing cells (Isl1 CKO). Although the early development of stato-acoustic ganglion was not affected by Isl1 deletion, at E14,5, we observed abnormalities in neuronal migration, formation of spiral ganglion and axon guidance in the Isl1 CKO cochlea. The length of the cochlear sensory epithelium was shortened by 20% as a consequence of lower proliferation activity of sensory precursor cells. Our results suggest that ISL1 is necessary for spiral ganglion formation and innervation of the Organ of Corti. Key words: transcription factor ISL1, neurons, Cre-loxP system, mouse model
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Transcriptional regulation in the development of neurosensory cells in the inner ear
Vochyánová, Simona ; Pavlínková, Gabriela (advisor) ; Schierová, Michaela (referee)
To understand the pathophysiology of hearing loss, it is necessary to identify genes responsible for specification and differentiation of sensory cells and neurons from a common neurosensory progenitor. These factors include LIM-homeodomain transcription factor ISLET1, high-mobility group protein SOX2, and basic helix-loop-helix transcription factors ATOH1, NEUROG1 and NEUROD1. This study aims to map important factors in inner ear development and their interactions with specific focus on transcription factor NEUROD1 and its role in mouse neurosensory inner ear development and function. Key words: inner ear, transcriptional regulation, mouse model, targeted deletion, embryonal development, Neurod1
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