Development and Regeneration of the Auditory Portion of the Inner Ear

The mammalian inner ear is an unusually complex organ comprising the vestibule, which is implicated in balance and equilibrium, and the coiled cochlea, containing the auditory machinery necessary for hearing, including the organ of Corti, the spiral ganglion, and the stria vascularis. Deafness commonly results from a lesion of the sensory cells and/or of the neurons of the auditory part of the inner ear, and there are currently no treatments designed to halt or reverse the progression of hearing loss. One of the promising technologies that could at least partially restore hearing is hair cell regeneration. Therefore, our main goal is to better understand how the development of the cochlea is regulated. Often indeed, the same molecules that control organogenesis during development also contribute to tissue regeneration after trauma, and this holds true in the inner ear as well. In parallel, the prevention of auditory sensory loss has also been investigated. To bridge the gap between animal models and human pathophysiology, we also focus our work on human 3D inner ear organoids, which provide a unique platform to study disease mechanisms and regenerative processes in a human-specific context.

human 3D inner ear organoids

Our laboratory employs a three-dimensional inner ear organoid model to investigate the mechanisms governing cellular development and the response of auditory cell types to genetic perturbations. Using a well-established differentiation protocol, these cultures generate hair cells, supporting cells, and neurons within 60 to 90 days.

We have established CRISPR/Cas9-based strategies to introduce fluorescent reporter tags such as tdTomato or GFP into specific loci, enabling the visualization and lineage tracing of distinct inner ear cell populations within human organoids. In parallel, we can manipulate gene expression through targeted loss- or gain-of-function approaches to model human pathologies in vitro. This combined strategy allows us to dissect the role of key genes implicated in hearing function and to elucidate their contribution to inner ear development, homeostasis, and disease.

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