title: Promotion of cortico-cerebral precursors expansion by artificial pri-miRNAs targeted against the Emx2 locus.
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.
authors: International School for Advanced Studies SISSA/ISAS, Trieste, Italy.
authors: Assunta
authors: A
authors: Diodato
authors: Moira
authors: M
authors: Pinzan
authors: Marilena
authors: M
authors: Granzotto
authors: Antonello
authors: A
authors: Mallamaci
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins