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Indulekha, C L and Divya, T S and Divya, M S and Sanalkumar, R and Abdul Rasheed, V and Dhanesh, S B and Anu , Sebin and Amitha, George and Jackson, James (2012) Hes-1 regulates the excitatory fate of neural progenitors through modulation of Tlx3 (HOX11L2) expression. Cellular and molecular life sciences : CMLS, 69 (4). pp. 611-627. ISSN 1420-9071

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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.

Item Type: Article
Uncontrolled Keywords: Notch signalingTlx3Glutamatergic differentiationHes-1Neural differentiation
Subjects: Neuro Stem Cell Biology
Depositing User: Central Library RGCB
Date Deposited: 27 Feb 2017 04:38
Last Modified: 04 Jul 2019 07:05
URI: http://rgcb.sciencecentral.in/id/eprint/263

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