Vliv ISL1 na vývoj neurosenzorických buněk vnitřního ucha

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