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Elp3 acetyl-transferase controls neuronal survival in the developing inner ear and is crucial to balance and hearing
Delacroix, Laurence
201610th Molecular Biology of Hearing and Deafness Conference
 

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Keywords :
hearing; development; inner ear
Abstract :
[en] Elp3 lysine acetyl-transferase, the catalytic subunit of the Elongator complex, has been assigned multiple roles in gene transcription, DNA methylation and protein translation efficiency. Given the importance of acetylation homeostasis in controlling developmental processes together with recent reports implicating Elp3 in cortical neurogenesis, we investigated its role during inner ear formation. In the inner ear, we detected Elp3 transcript in the sensory epithelia of the entire otic vesicle at embryonic day E11.5. At later stages, Elp3 mRNA is strongly expressed in the vestibular and spiral ganglion neurons. To investigate the role of Elp3 in vivo, we used a conditional knock-out mice (Foxg1Cre) in which the expression of the acetyl-transferase is lost in early otocyst. These mice show obvious vestibular defects as indicated by a stereotyped circling ambulation, head bobbing, retropulsion and the absence of a reaching response in the tail-hanging test. Furthermore, we identified a severe hearing loss in Elp3cKO mice through Auditory Brainstem Responses. We show that Elp3 enzyme is crucial for neuronal survival in the spiral ganglion and in the vestibule and that it ensures a correct innervation pattern in the developing inner ear. In the absence of Elp3, a drastic increase in the number of apoptotic neurons was detected by active Caspase-3 and pH2AX immunostainings, particularly during the early stages of development (between E12.5 and E14.5). Postnatally, the neurons remaining in Elp3cKO cochleae seem to establish synaptic contacts with the sensory cells but show obvious signs of cell damage as evidenced by Transmission Electron Microscopy. Taken together, these data support a role for Elp3 in hearing and balance and point out an important role for acetylation homeostasis during inner ear formation. We are currently investigating the molecular mechanisms underlying Elp3 effect on neuronal survival and pathfinding.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Delacroix, Laurence ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Elp3 acetyl-transferase controls neuronal survival in the developing inner ear and is crucial to balance and hearing
Publication date :
2016
Event name :
10th Molecular Biology of Hearing and Deafness Conference
Event place :
Hinxton, United Kingdom
Event date :
May 17-20
Audience :
International
Available on ORBi :
since 05 July 2016

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