title: Sox2 induces neuronal formation in the developing mammalian cochlea.
abstract: In the cochlea, spiral ganglion neurons play a critical role in hearing as they form the relay between mechanosensory hair cells in the inner ear and cochlear nuclei in the brainstem. The proneural basic helix-loop-helix transcription factors Neurogenin1 (Neurog1) and NeuroD1 have been shown to be essential for the development of otocyst-derived inner ear sensory neurons. Here, we show neural competence of nonsensory epithelial cells in the cochlea, as ectopic expression of either Neurog1 or NeuroD1 results in the formation of neuronal cells. Since the high-mobility-group type transcription factor Sox2, which is also known to play a role in neurogenesis, is expressed in otocyst-derived neural precursor cells and later in the spiral ganglion neurons along with Neurog1 and NeuroD1, we used both gain- and loss-of-function experiments to examine the role of Sox2 in spiral ganglion neuron formation. We demonstrate that overexpression of Sox2 results in the production of neurons, suggesting that Sox2 is sufficient for the induction of neuronal fate in nonsensory epithelial cells. Furthermore, spiral ganglion neurons are absent in cochleae from Sox2(Lcc/Lcc) mice, indicating that Sox2 is also required for neuronal formation in the cochlea. Our results indicate that Sox2, along with Neurog1 and NeuroD1, are sufficient to induce a neuronal fate in nonsensory regions of the cochlea. Finally, we demonstrate that nonsensory cells within the cochlea retain neural competence through at least the early postnatal period.
authors.affiliation: Section on Developmental Neuroscience and Section on Synaptic Transmission, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. puligillac@nidcd.nih.gov
authors.forename: Chandrakala
authors.initials: C
authors.lastname: Puligilla
authors.forename: Alain
authors.initials: A
authors.lastname: Dabdoub
authors.forename: Stephan D
authors.initials: SD
authors.lastname: Brenowitz
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kelley
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001703:Biophysics / Q000379:methods; D002454:Cell Differentiation; D003051:Cochlea / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D055748:SOXB1 Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D013136:Spiral Ganglion / Q000166:cytology; D014404:Tubulin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; D014404:Tubulin; C501008:Neurod1 protein, mouse; C527783:Sox2 protein, mouse; C462941:beta3 tubulin, mouse; C485184:enhanced green fluorescent protein; C486336:Neurog1 protein, mouse