Her6 regulates the neurogenetic gradient and neuronal identity in the thalamus.
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.
Scholpp
Steffen
S
MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, United Kingdom. steffen.scholpp@kit.edu
Delogu
Alessio
A
Gilthorpe
Jonathan
J
Peukert
Daniela
D
Schindler
Simone
S
Lumsden
Andrew
A
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013788:Thalamus / Q000166:cytology* / Q000502:physiology; D015027:Zebrafish / Q000033:anatomy & histology / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D011993:Recombinant Fusion Proteins; D029961:Zebrafish Proteins; C426854:Her6 protein, zebrafish; C486337:neurog1 protein, zebrafish