| RRC ID |
43564
|
| Author |
Indulekha CL, Divya TS, Divya MS, Sanalkumar R, Rasheed VA, Dhanesh SB, Sebin A, George A, James J.
|
| Title |
Hes-1 regulates the excitatory fate of neural progenitors through modulation of Tlx3 (HOX11L2) expression.
|
| Journal |
Cell Mol Life Sci
|
| 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.
|
| Volume |
69(4)
|
| Pages |
611-27
|
| Published |
2012-2-1
|
| DOI |
10.1007/s00018-011-0765-8
|
| PMID |
21744064
|
| MeSH |
Amino Acid Sequence
Animals
Basic Helix-Loop-Helix Transcription Factors / chemistry
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Binding Sites
Cell Differentiation
Cell Line
DNA / metabolism
Embryonic Stem Cells / cytology
Gene Expression Regulation*
Glutamic Acid / pharmacology
Homeodomain Proteins / chemistry
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Mice
Molecular Sequence Data
Neural Stem Cells / cytology*
Neural Stem Cells / metabolism
Neurons / metabolism
Promoter Regions, Genetic
Protein Binding
Protein Structure, Tertiary
Signal Transduction
Transcription Factor HES-1
gamma-Aminobutyric Acid / pharmacology
|
| IF |
6.496
|
| Times Cited |
11
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
IMR-32(RCB1895) |
