Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates
| Autor: | Fatih Semerci, Hsin-I Jen, Christine R. Norton, Hongyuan Zhang, Rogers M. Brown, Mirjana Maletic-Savatic, Thomas Gridley, Neil Segil, Renée K. Edlund, Martin L. Basch, Angelika Doetzlhofer, Susan E. Cole, Frederic Depreux, Andrew K. Groves |
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| Rok vydání: | 2016 |
| Předmět: |
inner ear
0301 basic medicine Notch Mouse QH301-705.5 Science cochlea Notch signaling pathway Biology hair cell General Biochemistry Genetics and Molecular Biology LFNG Mice 03 medical and health sciences Fate mapping Lateral inhibition otorhinolaryngologic diseases medicine Animals Inner ear Biology (General) Organ of Corti Cochlea Receptors Notch General Immunology and Microbiology General Neuroscience Glycosyltransferases Proteins Cell Biology General Medicine Anatomy Cell biology Developmental Biology and Stem Cells 030104 developmental biology medicine.anatomical_structure Glucosyltransferases lateral inhibition Mutation Medicine Fringe sense organs Hair cell Signal Transduction Research Article |
| Zdroj: | eLife, Vol 5 (2016) eLife |
| ISSN: | 2050-084X |
| Popis: | 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. DOI: http://dx.doi.org/10.7554/eLife.19921.001 |
| Databáze: | OpenAIRE |
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