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Her6 regulates the neurogenetic gradient and neuronal identity in the thalamus
MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London, United Kingdom. (Institute of Toxicology and Genetics, Institute of Technology Karlsruhe, Postfach 3640, 76021 Karlsruhe, Germany)
MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London, United Kingdom.
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London, United Kingdom)
MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London, United Kingdom. (Institute of Toxicology and Genetics, Institute of Technology Karlsruhe, Postfach 3640, 76021 Karlsruhe, Germany)
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2009 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 47, 19895-19900 p.Article in journal (Refereed) Published
Abstract [en]

During vertebrate brain development, the onset of neuronal differentiation is under strict temporal control. In the mammalian thalamus and other brain regions, neurogenesis is regulated also in a spatially progressive manner referred to as a neurogenetic gradient, the underlying mechanism of which is unknown. Here we describe the existence of a neurogenetic gradient in the zebrafish thalamus and show that the progression of neurogenesis is controlled by dynamic expression of the bHLH repressor her6. Members of the Hes/Her family are known to regulate proneural genes, such as Neurogenin and Ascl. Here we find that Her6 determines not only the onset of neurogenesis but also the identity of thalamic neurons, marked by proneural and neurotransmitter gene expression: loss of Her6 leads to premature Neurogenin1-mediated genesis of glutamatergic (excitatory) neurons, whereas maintenance of Her6 leads to Ascl1-mediated production of GABAergic (inhibitory) neurons. Thus, the presence or absence of a single upstream regulator of proneural gene expression, Her6, leads to the establishment of discrete neuronal domains in the thalamus.

Place, publisher, year, edition, pages
The National Academy of Sciences , 2009. Vol. 106, no 47, 19895-19900 p.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:umu:diva-43080DOI: 10.1073/pnas.0910894106PubMedID: 19903880OAI: oai:DiVA.org:umu-43080DiVA: diva2:411237
Available from: 2011-04-18 Created: 2011-04-18 Last updated: 2017-12-11Bibliographically approved

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Gilthorpe, Jonathan

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