In vivo overactivation of the Notch signaling pathway in the developing cochlear epithelium

Tomoko Tateya, Susumu Sakamoto, Itaru Imayoshi, Ryoichiro Kageyama
Hearing Research 2015, 327: 209-17
Notch signaling is thought to play important roles in both prosensory domain specification and cell fate determination during inner ear development. Inhibition of the Notch signaling pathway in prosensory cells results in excessive hair cell formation, while activation of the Notch signaling pathway by overexpression of activated Notch1 (Notch1-intercellular domain, NICD) in the cochlear epithelium results in ectopic sensory patches where NICD is expressed. However, the effect of Notch activation on the prosensory domain is not fully understood. To elucidate the precise roles of Notch signaling in cochlear prosensory epithelium we examined the effects of Notch overactivation on cochlear prosensory cells of transgenic mice with conditional NICD expression. The histology of the cochlear epithelium was investigated in these mice. The cochlear duct of conditional NICD embryos was wide and short, and the epithelium formed an abnormal tubular structure. Hair cell numbers were reduced though some hair cells developed where NICD was overexpressed. The decrease in hair cells was not accompanied by Hes5-positive and Prox1-positive supporting cell overproduction. Ectopic expression of early prosensory markers, such as Jag1 and Hes/Hey genes, was observed but no expression of Hes5 was found. Our data shows that NICD overexpression disrupts the extension of cochlear epithelium, and reduces the total numbers of hair cells and supporting cells in the sensory epithelium. Thus, an appropriate level of Notch signaling is needed for the normal extension of the cochlear epithelium and for differentiation of both hair cells and supporting cells.

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