Cochlear supporting cell transdifferentiation and integration into hair cell layers by inhibition of ephrin-B2 signalling.
In mammals, cochlear sensory hair cells that are responsible for hearing are postmitotic and are not replaced after loss. One of the most promising strategies to regenerate hair cells is to identify and inhibit the factors preventing the conversion of adjacent non-sensory supporting cells into hair cells. Here we demonstrate that mammalian hair cells can be directly generated from supporting cells by inhibition of ephrin-B2 signalling. Using either ephrin-B2 conditional knockout mice, shRNA-mediated gene silencing or soluble inhibitors, we found that downregulation of ephrin-B2 signalling at embryonic stages results in supporting cell translocation into hair cell layers and subsequent switch in cell identity from supporting cell to hair cell fate. As transdifferentiation is here a result of displacement across boundary, this original finding presents the interest that newly generated hair cells directly integrate either hair cell layer, then would be likely more rapidly able to fit into functional circuitry.
GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36, B-4000 Liège, Belgium.
Jean
J
Defourny
GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36, B-4000 Liège, Belgium.
Susana
S
Mateo Sánchez
Department of Neurosciences, Experimental Neurology, VIB - Vesalius Research Center, Laboratory of Neurobiology, KU Leuven - University of Leuven, B-3000 Leuven, Belgium.
Lies
L
Schoonaert
1] Department of Neurosciences, Experimental Neurology, VIB - Vesalius Research Center, Laboratory of Neurobiology, KU Leuven - University of Leuven, B-3000 Leuven, Belgium [2] Department of Neurology, University Hospitals Leuven, B-3000 Leuven, Belgium.
Wim
W
Robberecht
Center for Developmental Biology, University of Toulouse, CNRS, CBD UMR 5547, F-31062 Toulouse 9, France.
Alice
A
Davy
GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36, B-4000 Liège, Belgium.
Laurent
L
Nguyen
GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36, B-4000 Liège, Belgium.
Brigitte
B
Malgrange
D000818:Animals; D054338:Cell Transdifferentiation; D003051:Cochlea / Q000196:embryology* / Q000378:metabolism; D036388:Ephrin-B2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006198:Hair Cells, Auditory; D051379:Mice
D036388:Ephrin-B2