Unravelling the roles of lysine acetylation by Elp3 during inner ear development

Contact : Susana.MateoSanchez@student.ulg.ac.be ldelacroix@ulg.ac.be In conclusion, we have demonstrated the expression of Elp3 in the inner ear and pointed out a role for this acetyl-transferase in both audition and balance function. Our results clearly show the implication of Elp3 in ciliogenesis, hair cell innervation and neuronal survival and we plan to go deeper in the mechanisms involved through the identification of the proteins acetylated by Elp3. In order to identify Elp3-regulated genes, RNA-Seq experiments have been performed with wild-type and Elp3 cKO cochleae at stages E14.5 and E18.5. Interesting candidates have already been identified: transcription level of several kif (kinesin member family) genes was decreased in Elp3 cKO, which could explain ciliogenesis defects, as well as Ntrk1 (Neurotrophic tyrosine kinase receptor, type 1) gene expression, which could explain increased neuronal apoptosis in the Elp3 cKO spiral ganglion compared to wild-type littermates. The inner ear is composed of a vestibular part that controls balance, and the cochlea, which is dedicated to hearing. In both parts of the inner ear, sensory epithelia comprise supporting cells surrounding the sensory hair cells. These cells bear at their apical surface a staircase-structured hair bundle, consisting of multiple rows of actin-based stereocilia and a single tubulin-based kinocilium. This hair bundle allows the transduction from mechanical stimuli, initiated by sound or gravitational changes, to electrical signals that will then be transmitted by neurons from the spiral ganglion (innervating hair cells of the cochlea) or the vestibular ganglion. The inner ear organogenesis requires a tightly regulated transcriptional program that can be affected by post-transcriptional and post-translational modifications among which lysine acetylation. Given the importance of acetylation homeostasis in controlling developmental processes, we planned to investigate its role in inner ear formation and focused our attention on Elp3 acetyl-transferase, a member of the Elongator complex recently implicated in neurogenesis.