Assunta Diodato, Moira Pinzan, Marilena Granzotto and Antonello Mallamaci Pages 152 - 161 ( 10 )
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.
Emx2, cerebral cortex, RNAa, neural stem cell, neuronal progenitor, lentivector
Laboratory of Cerebral Cortex Development, SISSA - Neurobiology Sector, via Bonomea 265 - 34136 - Trieste – Italy.