Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/7177
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Type: Journal article
Title: Mouse orthologue of ARX, a gene mutated in several X-linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons
Author: Colombo, E.
Galli, R.
Cossu, G.
Gecz, J.
Broccoli, V.
Citation: Developmental Dynamics, 2004; 231(3):631-639
Publisher: Wiley-Liss
Issue Date: 2004
ISSN: 1058-8388
1097-0177
Statement of
Responsibility: 
Elena Colombo, Rossella Galli, Giulio Cossu, Jozef Gécz, Vania Broccoli
Abstract: Mutations in the human ARX gene show unusually heterogeneous clinical presentations, including syndromic and nonsyndromic mental retardation, myoclonic epilepsy with spasticity, and lissencephaly with abnormal genitalia, that are believed to arise from an impairment of the embryonic mechanisms building the anterior central nervous system structures. Here, we show that the murine ortholog Arx has a highly dynamic expression pattern during both early shaping of the forebrain vesicle and later major events of neural migrations and cell-type specification. Early on, the Arx gene is specifically activated in anterior forebrain anlage. Afterward, Arx expression is confined to the telencephalic vesicles and is enhanced during differentiation of the subpallial structures of the ganglionic eminences, overlapping with Dlx2, Dlx5, and Gad1 transcriptional domains. Tangentially migrating neurons reaching the cortical plate are also Arx-positive at all embryonic stages analyzed. RNA-protein colabeling staining shows that Arx expression is maintained in the mature cortical interneurons, suggesting its involvement in the different functions of the gamma-aminobutyric acid (GABA)ergic neurons settled into the adult cerebral cortex. Finally, Arx expression is detected in the anterior subventricular layer of the adult brain, where neural stem cells have been shown to be located. Of interest, Arx expression is highly up-regulated during in vitro differentiation of pure neural stem cell cultures retrieved from adult brain. All together, these findings suggest Arx as a gene involved in the commitment of proliferating neuroblasts into a GABAergic neuronal fate. In conclusion, our mouse Arx expression data provide important further insights into the puzzling complexity of the human ARX mutation pleiotropy.
Keywords: Prosencephalon; Neurons; Cells, Cultured; Stem Cells; Animals; Animals, Newborn; Humans; Mice; Epilepsy; Mental Retardation, X-Linked; gamma-Aminobutyric Acid; Homeodomain Proteins; Transcription Factors; Biological Markers; Culture Media; In Situ Hybridization; Cell Differentiation; Gene Expression Regulation, Developmental; Embryonic Development; Mutation
RMID: 0020041067
DOI: 10.1002/dvdy.20164
Appears in Collections:Paediatrics publications

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