Hes-1 regulates the excitatory fate of neural progenitors through modulation of <Emphasis Type="Italic">Tlx3 (HOX11L2)</Emphasis> expression |
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Authors: | Chandrasekharan?Lalitha?Indulekha Thulasi?Sheela?Divya Mundackal?Sivaraman?Divya Rajendran?Sanalkumar Vazhanthodi?Abdul?Rasheed Sivadasan?Bindu?Dhanesh Anu?Sebin Amitha?George Email author" target="_blank">Jackson?JamesEmail author |
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Institution: | (1) Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram, Kerala, 695 014, India; |
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Abstract: | Tlx3 (HOX11L2) is regarded as one of the selector genes in excitatory versus inhibitory fate specification of neurons in distinct regions
of the nervous system. Expression of Tlx3 in a post-mitotic immature neuron favors a glutamatergic over GABAergic fate. The
factors that regulate Tlx3 have immense importance in the fate specification of glutamatergic neurons. Here, we have shown that Notch target gene, Hes-1, negatively regulates Tlx3 expression, resulting in decreased generation of glutamatergic neurons. Down-regulation of Hes-1 removed the inhibition on Tlx3 promoter, thus promoting glutamatergic differentiation. Promoter–protein interaction studies
with truncated/mutated Hes-1 protein suggested that the co-repressor recruitment mediated through WRPW domain of Hes-1 has
contributed to the repressive effect. Our results clearly demonstrate a new and unique role for canonical Notch signaling
through Hes-1, in neurotransmitter/subtype fate specification of neurons in addition to its known functional role in proliferation/maintenance
of neural progenitors. |
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