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• W1994051569 startingPage "e15459" @default.
• W1994051569 abstract "Background Notch signalling plays a central role in the mechanisms regulating neuronal differentiation in the vertebrate nervous system. The transcriptional repressors encoded by Hes genes are the main effectors of this pathway, acting in neural progenitors during the lateral inhibition process to repress proneural genes and inhibit differentiation. However, Hes6 genes seem to behave differently: they are expressed in differentiating neurons and facilitate the activity of proneural genes in promoting neurogenesis. Still, the molecular mechanisms underlying this unique function of Hes6 genes are not yet understood. Methodology/Principal Findings Here, we identify two subgroups of Hes6 genes that seem conserved in most vertebrate species and characterize a novel Hes6 gene in chicken: cHes6-1. The embryonic expression pattern of cHes6-1 suggests roles for this gene in the formation of the pancreas, nervous system and in the generation of body asymmetry. We show that cHes6-1 is negatively regulated by Notch signalling in the developing embryonic spinal cord and in pancreatic progenitors, but requires Notch for the observed asymmetric expression at the lateral mesoderm. Functional studies by ectopic expression in the chick embryonic neural tube revealed that cHES6-1 up-regulates the expression of cDelta1 and cHes5 genes, in contrast with overexpression of cHES6-2, which represses the same genes. We show that this activity of cHES6-2 is dependent on its capacity to bind DNA and repress transcription, while cHES6-1 seems to function by sequestering other HES proteins and inhibit their activity as transcriptional repressors. Conclusions/Significance Our results indicate that the two chick HES6 proteins act at different phases of neuronal differentiation, contributing to the progression of neurogenesis by different mechanisms: while cHES6-2 represses the transcription of Hes genes, cHES6-1 acts later, sequestering HES proteins. Together, the two cHES6 proteins progressively shut down the Notch-mediated progenitor program and ensure that neuronal differentiation can proceed." @default.
• W1994051569 created "2016-06-24" @default.
• W1994051569 creator A5022631225 @default.
• W1994051569 creator A5077255106 @default.
• W1994051569 date "2010-12-02" @default.
• W1994051569 modified "2023-09-27" @default.
• W1994051569 title "HES6-1 and HES6-2 Function through Different Mechanisms during Neuronal Differentiation" @default.
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• W1994051569 doi "https://doi.org/10.1371/journal.pone.0015459" @default.
• W1994051569 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2996300" @default.
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