title: Delta/notch-like EGF-related receptor (DNER) is expressed in hair cells and neurons in the developing and adult mouse inner ear.
abstract: The Notch signaling pathway is known to play important roles in inner ear development. Previous studies have shown that the Notch1 receptor and ligands in the Delta and Jagged families are important for cellular differentiation and patterning of the organ of Corti. Delta/notch-like epidermal growth factor (EGF)-related receptor (DNER) is a novel Notch ligand expressed in developing and adult CNS neurons known to promote maturation of glia through activation of Notch. Here we use in situ hybridization and an antibody against DNER to carry out expression studies of the mouse cochlea and vestibule. We find that DNER is expressed in spiral ganglion neuron cell bodies and peripheral processes during embryonic development of the cochlea and expression in these cells is maintained in adults. DNER becomes strongly expressed in auditory hair cells during postnatal maturation in the mouse cochlea and immunoreactivity for this protein is strong in hair cells and afferent and efferent peripheral nerve endings in the adult organ of Corti. In the vestibular system, we find that DNER is expressed in hair cells and vestibular ganglion neurons during development and in adults. To investigate whether DNER plays a functional role in the inner ear, perhaps similar to its described role in glial maturation, we examined cochleae of DNER-/- mice using immunohistochemical markers of mature glia and supporting cells as well as neurons and hair cells. We found no defects in expression of markers of supporting cells and glia or myelin, and no abnormalities in hair cells or neurons, suggesting that DNER plays a redundant role with other Notch ligands in cochlear development.
authors.affiliation: Department of Biological Structure, University of Washington, 1959 NE Pacific St., Box 357420, Seattle, WA 98195, USA.
authors.forename: Byron H
authors.initials: BH
authors.lastname: Hartman
authors.forename: Branden R
authors.initials: BR
authors.lastname: Nelson
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Reh
authors.forename: Olivia
authors.initials: O
authors.lastname: Bermingham-McDonogh
mesh_terms: D000367:Age Factors; D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism; D009412:Nerve Fibers / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009457:Neuroglia / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D009476:Neurons, Efferent / Q000502:physiology; D009925:Organ of Corti / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D013136:Spiral Ganglion / Q000196:embryology / Q000254:growth & development / Q000502:physiology
chemical_list: C486765:Dner protein, mouse; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface