title: Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates.
abstract: The signals that induce the organ of Corti and define its boundaries in the cochlea are poorly understood. We show that two Notch modifiers,LfngandMfng,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 ofLfngandMfngdisrupts 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.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Basch
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Rogers M
authors.initials: RM
authors.lastname: Brown
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Jen
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Fatih
authors.initials: F
authors.lastname: Semerci
authors.affiliation: Department of Cell Biology and Anatomy, Rosalind Franklin University of Medicine and Science, Chicago, United States.
authors.forename: Frederic
authors.initials: F
authors.lastname: Depreux
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Renée K
authors.initials: RK
authors.lastname: Edlund
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Maine Medical Center Research Institute, Scarborough, United States.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Norton
authors.affiliation: Maine Medical Center Research Institute, Scarborough, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gridley
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, United States.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Cole
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, United States.
authors.forename: Angelika
authors.initials: A
authors.lastname: Doetzlhofer
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Program in Developmental Biology, Baylor College of Medicine, Houston, United States.|Department of Pediatrics, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, United States.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Maletic-Savatic
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States.
authors.forename: Neil
authors.initials: N
authors.lastname: Segil
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Program in Developmental Biology, Baylor College of Medicine, Houston, United States.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
authors.forename: Andrew K
authors.identifier: http://orcid.org/0000-0002-0784-7998
authors.initials: AK
authors.lastname: Groves
mesh_terms: D000818:Animals; D005964:Glucosyltransferases; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009925:Organ of Corti / Q000196:embryology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011506:Proteins; D051880:Receptors, Notch; D016695:Glycosyltransferases; D005964:Glucosyltransferases; C498392:Lfng protein, mouse; C486343:Mfng protein, mouse
keywords: Fringe; Notch; cell biology; cochlea; developmental biology; hair cell; inner ear; lateral inhibition; mouse; stem cells