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Hes-1 regulates the excitatory fate of neural progenitors through modulation of Tlx3 (HOX11L2) expression.

Publication Type : Journal Article

Publisher : Cellular and Molecular Life Sciences

Source : Cellular and Molecular Life Sciences, Volume 69, Issue 4, p.611-627 (2012)

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Keywords : amino acid sequence, Animals, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, cell differentiation, Cell Line, DNA, Embryonic Stem Cells, gamma-Aminobutyric Acid, Gene Expression Regulation, glutamic acid, Homeodomain Proteins, Humans, Mice, Molecular Sequence Data, Neural stem cells, Neurons, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, signal transduction, Transcription Factor HES-1

Campus : Amritapuri

School : School of Biotechnology

Department : biotechnology

Year : 2012

Abstract : pTlx3 (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./p

Cite this Research Publication : Dr. Indulekha C. L. Pillai, TS, D., MS, D., R, S., VA, R., SB, D., A, S., A, G., and J, J., “Hes-1 Regulates the Excitatory fate of Neural Progenitors through Modulation of Tlx3 (HOX11L2) Expression”, Cellular and Molecular Life Sciences, vol. 69, no. 4, pp. 611-627 , 2012.

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