Her6 regulates the neurogenetic gradient and neuronal identity in the thalamus

Scholpp, SteffenMRC 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 (författare)

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.

Delogu, AlessioMRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London, United Kingdom (författare)
Gilthorpe, Jonathan D.Umeå universitet,Umeå centrum för molekylär medicin (UCMM),MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London, United Kingdom(Swepub:umu)jogi0002 (författare)
Peukert, DanielaMRC 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 (författare)
Schindler, SimoneInstitute of Toxicology and Genetics, Institute of Technology Karlsruhe, Postfach 3640, 76021 Karlsruhe, Germany (författare)
Lumsden, AndrewMRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London, United Kingdom (författare)
MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London, United KingdomInstitute of Toxicology and Genetics, Institute of Technology Karlsruhe, Postfach 3640, 76021 Karlsruhe, Germany (creator_code:org_t)

Ingår i:Proceedings of the National Academy of Sciences of the United States of America: The National Academy of Sciences106:47, s. 19895-199000027-84241091-6490

Av författaren/redakt...: Scholpp, Steffen; Delogu, Alessio; Gilthorpe, Jonat ...; Peukert, Daniela; Schindler, Simon ...; Lumsden, Andrew

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