Poster (Scientific congresses and symposiums)
UNRAVELLING THE ROLES OF LYSINE ACETYLATION BY ELP3 DURING INNER EAR DEVELOPMENT
Mateo Sanchez, Susana; Delacroix, Laurence; Freeman, Stephen et al.
2015Belgian Society for Cell and Developmental Biology (BSCDB)
 

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Keywords :
inner ear; Elongator; development
Abstract :
[en] Given the importance of acetylation homeostasis in controlling developmental processes [1-3], 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 [4]. To determine the role of Elp3 in the inner ear, we first analysed the spatio-temporal pattern of ELp3 mRNA expression and showed that it was expressed in the entire early otocyst at E11.5 and persisted later in the sensory epithelium of the cochlea (the organ of Corti), in the spiral ganglion, in the stria vascularis and in the vestibule. To unravel in vivo functions of Elp3 in the inner ear, we used conditional knock-out mice in which Elp3 gene is deleted from early otocyst (Elp3 cKO). We submitted these mice to a battery of vestibular testing (i.e. stereotyped circling ambulation, head bobbing, retropulsion, and absence of reaching response in the tail-hanging test) and found significant abnormalities. Besides, the auditory brain stem response of Elp3 cKO indicated that these mice are severely deaf. At the cellular level, we did not find any structural abnormalities nor cell patterning defects that could explain deafness or balance dysfunction in Elp3 cKO mice. However, we detected some defaults in the planar orientation of their auditory hair cell bundle. We were also able to demonstrate an increased level of apoptosis in the Elp3 cKO spiral ganglion at E14.5 leading to a reduced number of neurons and fibers innervating the cochlear hair cells as well as a reduced number of their synaptic ribbons at P15. Moreover, the remaining spiral ganglion neurons extend processes showing clearly defects regarding hair cells innervation (misorientation of fibers). In conclusion, our results clearly show a role for Elp3 both in hearing and balance. We plan to go deeper in the mechanisms involved through the identification of the proteins that are targeted for acetylation by Elp3.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Otolaryngology
Biochemistry, biophysics & molecular biology
Author, co-author :
Mateo Sanchez, Susana ;  Université de Liège > Département des sciences cliniques > Neurologie
Delacroix, Laurence ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Freeman, Stephen ;  Université de Liège > GIGA - Neurosciences
Laguesse, Sophie
Huysseune, Sandra ;  Université de Liège > Département des sciences cliniques > Neurologie
Delrez, Sophie ;  Université de Liège - ULiège > 3e an. méd.
Chariot, Alain ;  Université de Liège > Département de pharmacie > Chimie médicale
Nguyen, Laurent  ;  Université de Liège > GIGA - Neurosciences
Malgrange, Brigitte  ;  Université de Liège > GIGA - Neurosciences
Language :
English
Title :
UNRAVELLING THE ROLES OF LYSINE ACETYLATION BY ELP3 DURING INNER EAR DEVELOPMENT
Publication date :
06 June 2015
Event name :
Belgian Society for Cell and Developmental Biology (BSCDB)
Event date :
le 06 juin 2015
Audience :
International
Available on ORBi :
since 10 June 2015

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