TY - JOUR TI - Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates AU - Basch, Martin L AU - Brown, Rogers M, II AU - Jen, Hsin-I AU - Semerci, Fatih AU - Depreux, Frederic AU - Edlund, Renée K AU - Zhang, Hongyuan AU - Norton, Christine R AU - Gridley, Thomas AU - Cole, Susan E AU - Doetzlhofer, Angelika AU - Maletic-Savatic, Mirjana AU - Segil, Neil AU - Groves, Andrew K A2 - Whitfield, Tanya T VL - 5 PY - 2016 DA - 2016/12/14 SP - e19921 C1 - eLife 2016;5:e19921 DO - 10.7554/eLife.19921 UR - https://doi.org/10.7554/eLife.19921 AB - The signals that induce the organ of Corti and define its boundaries in the cochlea are poorly understood. We show that two Notch modifiers, Lfng and Mfng, are transiently expressed precisely at the neural boundary of the organ of Corti. Cre-Lox fate mapping shows this region gives rise to inner hair cells and their associated inner phalangeal cells. Mutation of Lfng and Mfng disrupts this boundary, producing unexpected duplications of inner hair cells and inner phalangeal cells. This phenotype is mimicked by other mouse mutants or pharmacological treatments that lower but not abolish Notch signaling. However, strong disruption of Notch signaling causes a very different result, generating many ectopic hair cells at the expense of inner phalangeal cells. Our results show that Notch signaling is finely calibrated in the cochlea to produce precisely tuned levels of signaling that first set the boundary of the organ of Corti and later regulate hair cell development. KW - inner ear KW - cochlea KW - Notch KW - hair cell KW - Fringe KW - lateral inhibition JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -