Reference : The Inhibition of Cyclin-Dependent Kinases Induces Differentiation of Supernumerary Hair...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/29254
The Inhibition of Cyclin-Dependent Kinases Induces Differentiation of Supernumerary Hair Cells and Deiters' Cells in the Developing Organ of Corti
English
Malgrange, Brigitte mailto [Université de Liège - ULg > > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc. >]
Knockaert, Marie [> > > >]
Belachew, Shibeshih mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie >]
Nguyen, Laurent mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie >]
Moonen, Gustave mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie - Doyen de la Faculté de Médecine]
Meijer, Laurent [> > > >]
Lefèbvre, Philippe mailto [Université de Liège - ULg > Département des sciences cliniques > Oto-rhino-laryngologie et audiophonologie >]
Nov-2003
FASEB Journal
17
14
2136-8
Yes (verified by ORBi)
International
0892-6638
1530-6860
[en] inner ear ; cochlea ; cdk ; regeneration ; hair cells
[en] In the embryonic day 19 organs of Corti, we showed that roscovitine, a chemical inhibitor of cyclin-dependent kinases (CDKs), significantly increased the number of hair cells (HCs) and corresponding supporting cells (SCs) by triggering differentiation of precursor cells without interacting with cell proliferation. The effect of roscovitine was mimicked by other CDK1, 2, 5, and 7 inhibitors but not by CDK4/6 and mitogen-activated protein kinase pathway antagonists. Immunohistochemical analysis indicated that roscovitine-specific intracellular targets, CDK1, 2, 5, and 7, were expressed in the organ of Corti and especially in Hensen's cells. Affinity chromatography studies showed a tight correlation between the protein levels of CDK1/2 and 5 and the rate of roscovitine-induced supernumerary cells in the organ of Corti. In addition, we demonstrated that basal CDK activity was higher and more roscovitine-sensitive at developmental stages that are selectively permissive for the emergence of supernumerary cells. These results suggest that CDKs are involved in the normal development of the organ of Corti and that, at least in E19 embryos, inhibition of CDKs is sufficient to trigger the differentiation of HCs and corresponding SCs, presumably from the Hensen's cell progenitors and/or from progenitors located in the greater epithelial ridge area.
Giga-Neurosciences
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS
Researchers ; Professionals
http://hdl.handle.net/2268/29254
10.1096/fj.03-0035fje

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