Emx2 encodes for a transcription factor controlling several aspects of cerebral cortex development. Its overexpression promotes self-renewal of young cortico-cerebral precursors, it promotes neuronal rather than gliogenic fates and it protects neuronal progenitors from cell death. These are all key activities for purposes of gene-promoted brain repair. Artificial pri-miRNAs targeting non-coding cis-active modules and/or conserved sequences of the Emx2 locus were delivered to embryonic cortico-cerebral precursors, by lentiviral vectors. A subset of these pri-miRNAs upregulated Emx2, possibly stimulating its transcription. That led to enhanced self-renewal, delayed differentiation and reduced death of neuronally committed precursors, resulting in an appreciable expansion of the neuronogenic precursors pool. This method makes Emx2 overexpression for purposes of brain repair a more feasible goal, avoiding the drawbacks of exogenous gene copies introduction. Interestingly, the two genomic enhancers targeted by these pri-miRNAs were discovered to be naturally transcribed. Their expression profile suggests their possible involvement in regulation of Emx2 transcription.
Promotion of cortico-cerebral precursors expansion by artificial pri-miRNAs targeted against the Emx2 locus / Diodato, A; Pinzan, M; Granzotto, M; Mallamaci, Antonio. - In: CURRENT GENE THERAPY. - ISSN 1566-5232. - 13:2(2013), pp. 152-161. [10.2174/1566523211313020009]
Promotion of cortico-cerebral precursors expansion by artificial pri-miRNAs targeted against the Emx2 locus.
Mallamaci, Antonio
2013-01-01
Abstract
Emx2 encodes for a transcription factor controlling several aspects of cerebral cortex development. Its overexpression promotes self-renewal of young cortico-cerebral precursors, it promotes neuronal rather than gliogenic fates and it protects neuronal progenitors from cell death. These are all key activities for purposes of gene-promoted brain repair. Artificial pri-miRNAs targeting non-coding cis-active modules and/or conserved sequences of the Emx2 locus were delivered to embryonic cortico-cerebral precursors, by lentiviral vectors. A subset of these pri-miRNAs upregulated Emx2, possibly stimulating its transcription. That led to enhanced self-renewal, delayed differentiation and reduced death of neuronally committed precursors, resulting in an appreciable expansion of the neuronogenic precursors pool. This method makes Emx2 overexpression for purposes of brain repair a more feasible goal, avoiding the drawbacks of exogenous gene copies introduction. Interestingly, the two genomic enhancers targeted by these pri-miRNAs were discovered to be naturally transcribed. Their expression profile suggests their possible involvement in regulation of Emx2 transcription.File | Dimensione | Formato | |
---|---|---|---|
Diodato et al_Current Gene Therapy 2013_Supplem Mater.pdf
non disponibili
Tipologia:
Altro materiale allegato
Licenza:
Non specificato
Dimensione
701.59 kB
Formato
Adobe PDF
|
701.59 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Diodato et al_Current Gene Therapy 2013_Article.pdf
non disponibili
Tipologia:
Versione Editoriale (PDF)
Licenza:
Non specificato
Dimensione
1.36 MB
Formato
Adobe PDF
|
1.36 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.