Role of NEUROD1 transcriptional network on the development and function of inner ear neurons

Identification of transcription factors involved in a complex network regulating the development of neurosensory cells in the inner ear is a key point for understanding the pathophysiology of hearing loss, development of new therapeutic tools, and for hearing loss prevention. The aim of this thesis was to elucidate the function of the transcription factor NEUROD1 in the development of the inner ear and sensory neurons. Using the Cre-loxP recombination system, a unique mouse model was created with tissue-specific deletion of Neurod1 in NEUROD1-Cre positive cells (Neurod1ST). In the inner ear, Neurod1 was deleted only in neurons permitting to identify the secondary effects of Neurod1 elimination in neurons on sensory cell development. We showed that neither the early development of the inner ear nor the formation of the statoacoustic ganglia was significantly affected by Neurod1 deletion. The primary consequence of the deletion was manifested by increased neuronal death due to apoptosis, which resulted in a reduced number of differentiated neurons in the inner ear. Spiral and vestibular ganglia were smaller in the mutants, and there was a number of neurons misplaced, indicating impaired migration. The cochlear sensory epithelium was shortened probably due to the reduced number of neurons within the..