Research

Otic Placode Morphogenesis

The inner ear is one of the most complex three-dimensinal organs of our head, however it is still little understood how cells organize during development to generate this complex organ. We are studying several morphogenetic events to understand the interaction between cell polarity, cell remodeling, migration and cytoskeleton rearrangements with mechanical properties and signalling cues. 

Otic precursors are initially not organized, cells have arounded shape and progressively orient and elongate to form a ordered epithelium in a MET process. The sequence of events involving the establishment of apical polarity, microtubule orientation, actomyosion activation, ECM and rosette formation is unknown. We aim to understand the cellular and molecular events during placode formation and the biomechanics driving the formation of an ellipsoidal placode.

Hair Cell innervation and Mechanosensory circuit formation

We are interested in understanding how SAG axons are guided towards inner ear hair cells and how otic neuroblasts coalesce into a proper shaped ganglion.  Little is known on the molecules involved in establishing the mechanosensory circuit and projection to the brain. We are addressing all these questions by high spatiotemporal imaging and functional experiments of candidate cues.

Transcription factors and chromatin remodelling in otic neuron identity 

The identification of TF driving neuronal differentiation and subtype sensory identities is crucial for regenerative medicine therapies and for the understanding the basis of sensory diseases. Compared to the central nervous system and the development of hair cells, very little is known of how the transition from inner ear neuronal precursors to differentiated neurons is achieved at the molecular level. What makes an otic sensory neuron different from a nociceptor or chemosensory neuron?

We aim at identifying which TFs are key in otic sensory neuronal identity and maintaning their terminal features, together with the analysis of the  chromatin remodelling events regulating  the difference between distict sensory neuronal subtypes. 

Human inner ear organoids for studying mutations causing hearing loss 

Several mutations either in the coding regions or regulatory elements have been linked to hearing loss, vertigo or neuropathies. In some instances, the sensory disease is not due to a malfunctioning protein but to a reduction/increased of expression or epigenetic modifications of the affected loci. Those mutations might be rescued by modification of the expression levels using the crispr system. We are testing the use of the cripr system to revert regulatory mutations using human inner ear organoids.