title: Progression of neurogenesis in the inner ear requires inhibition of Sox2 transcription by neurogenin1 and neurod1.
abstract: Sox2 is required for proper neuronal formation in the CNS, but the molecular mechanisms involved are not well characterized. Here, we addressed the role of Sox2 in neurogenesis of the developing chicken inner ear. Overexpressing Sox2 from a constitutive (β-actin) promoter induces the expression of the proneural gene, Neurogenin1 (Ngn1); however, the expression of a downstream target of Ngn1, Neurod1, is unchanged. As a result, there is a reduction of neural precursors to delaminate and populate the developing cochleo-vestibular ganglion. In contrast, overexpression of either Ngn1 or Neurod1 is sufficient to promote the neural fate in this system. These results suggest that high levels of Sox2 inhibit progression of neurogenesis in the developing inner ear. Furthermore, we provide evidence that Ngn1 and Neurod1 inhibit Sox2 transcription through a phylogenetically conserved Sox2 enhancer to mediate neurogenesis. We propose that Sox2 confers neural competency by promoting Ngn1 expression, and that negative feedback inhibition of Sox2 by Ngn1 is an essential step in the progression from neural precursor to nascent neuron.
authors: National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA.
authors: Lale
authors: L
authors: Evsen
authors: Satoko
authors: S
authors: Sugahara
authors: Masanori
authors: M
authors: Uchikawa
authors: Hisato
authors: H
authors: Kondoh
authors: Doris K
authors: DK
authors: Wu
mesh_terms: D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D002642:Chick Embryo; D007758:Ear, Inner / Q000166:cytology* / Q000196:embryology; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009433:Neural Inhibition / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; D014404:Tubulin; C413663:fluorescent protein 583; C093564:Neurogenic differentiation factor 1; C486336:Neurog1 protein, mouse