title: Hes-1 regulates the excitatory fate of neural progenitors through modulation of Tlx3 (HOX11L2) expression.
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.
authors: Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram, Kerala, 695 014, India.
authors: Chandrasekharan Lalitha
authors: CL
authors: Indulekha
authors: Thulasi Sheela
authors: TS
authors: Divya
authors: Mundackal Sivaraman
authors: MS
authors: Divya
authors: Rajendran
authors: R
authors: Sanalkumar
authors: Vazhanthodi Abdul
authors: VA
authors: Rasheed
authors: Sivadasan Bindu
authors: SB
authors: Dhanesh
authors: Anu
authors: A
authors: Sebin
authors: Amitha
authors: A
authors: George
authors: Jackson
authors: J
authors: James
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D018698:Glutamic Acid; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; D005680:gamma-Aminobutyric Acid; C489734:Hes1 protein, mouse; C487377:Tlx3 protein, mouse