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Titolo:
Conserved function of Caenorhabditis elegans UNC-30 and mouse Pitx2 in controlling GABAergic neuron differentiation
Autore:
Westmoreland, JJ; McEwen, J; Moore, BA; Jin, YS; Condie, BG;
Indirizzi:
Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA Med Coll Georgia Augusta GA USA 30912 Med & Genet, Augusta, GA 30912 USA Med Coll Georgia, Dept Med, Augusta, GA 30912 USA Med Coll Georgia Augusta GA USA 30912 ia, Dept Med, Augusta, GA 30912 USA Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA Med Coll Georgia Augusta GA USA 30912 Biol & Anat, Augusta, GA 30912 USA Univ Calif Santa Cruz, Dept Mol Cellular & Dev Biol, Santa Cruz, CA 95064 USA Univ Calif Santa Cruz Santa Cruz CA USA 95064 l, Santa Cruz, CA 95064 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 17, volume: 21, anno: 2001,
pagine: 6810 - 6819
SICI:
0270-6474(20010901)21:17<6810:CFOCEU>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTAMIC-ACID DECARBOXYLASE; GLUTATHIONE-S-TRANSFERASE; MESENCEPHALIC DOPAMINERGIC-NEURONS; GAMMA-AMINOBUTYRIC-ACID; HUMAN OTX GENES; C-ELEGANS; HOMEODOMAIN PROTEIN; HOMEOBOX GENE; ESCHERICHIA-COLI; RIEGER-SYNDROME;
Keywords:
glutamate decarboxylase; neuron differentiation; Gad67; Gad1; unc-30; Pitx2; GABAergic neuron; mouse development; C. elegans;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
75
Recensione:
Indirizzi per estratti:
Indirizzo: Condie, BG Med Coll Georgia, Inst Mol Med & Genet, 1120 15th St CB2803, Augusta, GA 30912 USA Med Coll Georgia 1120 15th St CB2803 Augusta GA USA 30912 2 USA
Citazione:
J.J. Westmoreland et al., "Conserved function of Caenorhabditis elegans UNC-30 and mouse Pitx2 in controlling GABAergic neuron differentiation", J NEUROSC, 21(17), 2001, pp. 6810-6819

Abstract

We are taking a cross-species approach to identify genes that are requiredfor mammalian GABAergic neuron differentiation. On the basis of homeodomain similarity, the vertebrate Pitx genes appear to be orthologs of unc-30, aCaenorhabditis elegans gene necessary for differentiation of the GABAergicphenotype of type D neurons. One of the Pitx genes, Pitx2, is expressed inregions of GABAergic neurogenesis in the mammalian brain. These observations led us to test the functional conservation of the mouse Pitx2 and worm unc-30 genes using a rescue assay. Pitx2 rescues the GABAergic differentiation defect and partially rescues the axon guidance and behavioral phenotypesof unc-30 mutants, indicating a high degree of functional conservation between these evolutionarily related genes. Previous studies show that UNC-30 directly regulates the unc-25/glutamate decarboxylase gene that encodes theenzyme for GABA synthesis. We find that the promoter regions of the mouse and human genes coding for the 67 kDa glutamate decarboxylase (Gad1) also contain binding sites matching the UNC-30/Pitx2 consensus binding site sequence. We show that these sites specifically bind to Pitx2 protein in vitro and that in transfected neuroblastoma cells, the Pitx2 binding sites contribute to the basal activity of the Gad1 promoter. Furthermore, in cotransfection experiments, we find that Pitx2 strongly activates the Gad1 promoter. These results indicate that Pitx2 may regulate Gad1 expression in mammals, suggesting a new role for this key developmental transcription factor as a regulator of GABAergic differentiation during mammalian neural development. Our results suggest that some of the mechanisms regulating GABAergic differentiation are evolutionarily conserved.

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Documento generato il 10/04/20 alle ore 02:02:30