Cochlear supporting cell transdifferentiation and integration into hair cell layers by inhibition of ephrin-B2 signalling

Jean Defourny, Susana Mateo Sánchez, Lies Schoonaert, Wim Robberecht, Alice Davy, Laurent Nguyen and Brigitte Malgrange ()
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Jean Defourny: GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36, B-4000 Liège, Belgium
Susana Mateo Sánchez: GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36, B-4000 Liège, Belgium
Lies Schoonaert: Experimental Neurology, VIB - Vesalius Research Center, Laboratory of Neurobiology, KU Leuven - University of Leuven
Wim Robberecht: Experimental Neurology, VIB - Vesalius Research Center, Laboratory of Neurobiology, KU Leuven - University of Leuven
Alice Davy: Center for Developmental Biology, University of Toulouse, CNRS
Laurent Nguyen: GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36, B-4000 Liège, Belgium
Brigitte Malgrange: GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36, B-4000 Liège, Belgium

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms8017

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