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Hes6 Is Required for the Neurogenic Activity of Neurogenin and NeuroD

Public Library of Science
Publication Date
DOI: 10.1371/journal.pone.0027880
  • Research Article
  • Biology
  • Biochemistry
  • Neurochemistry
  • Neurogenesis
  • Developmental Biology
  • Cell Differentiation
  • Model Organisms
  • Animal Models
  • Xenopus Laevis
  • Molecular Cell Biology
  • Signal Transduction
  • Signaling In Selected Disciplines
  • Developmental Signaling
  • Neuroscience
  • Developmental Neuroscience
  • Biology


In the embryonic neural plate, a subset of precursor cells with neurogenic potential differentiates into neurons. This process of primary neurogenesis requires both the specification of cells for neural differentiation, regulated by Notch signaling, and the activity of neurogenic transcription factors such as neurogenin and NeuroD which drive the program of neural gene expression. Here we study the role of Hes6, a member of the hairy enhancer of split family of transcription factors, in primary neurogenesis in Xenopus embryos. Hes6 is an atypical Hes gene in that it is not regulated by Notch signaling and promotes neural differentiation in mouse cell culture models. We show that depletion of Xenopus Hes6 (Xhes6) by morpholino antisense oligonucleotides results in a failure of neural differentiation, a phenotype rescued by both wild type Xhes6 and a Xhes6 mutant unable to bind DNA. However, an Xhes6 mutant that lacks the ability to bind Groucho/TLE transcriptional co-regulators is only partly able to rescue the phenotype. Further analysis reveals that Xhes6 is essential for the induction of neurons by both neurogenin and NeuroD, acting via at least two distinct mechanisms, the inhibition of antineurogenic Xhairy proteins and by interaction with Groucho/TLE family proteins. We conclude Xhes6 is essential for neurogenesis in vivo, acting via multiple mechanisms to relieve inhibition of proneural transcription factor activity within the neural plate.

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