Tracking and transforming neocortical progenitors by CRISPR/Cas9 gene targeting and PiggyBac transposase lineage labeling

• DOI: 10.1242/dev.118836
• Publication Date: 2015-09-24T02:23:52Z
• Authors: Fuyi Chen; Joel Rosiene; Alicia Che; Albert Becker; Joseph LoTurco
• Keywords: Transposase

The ability to induce targeted mutations in somatic cells developing organisms and then track the fates of those is a powerful approach both for studying neural development modeling human disease. CRISPR/Cas9 system allows such mutagenesis, we therefore tested it combination with piggyBac transposase lineage labeling neocortical progenitors genes linked neurodevelopmental disruptions tumor formation. We show that sgRNAs designed target PTEN successfully decreased expression, led neuronal hypertrophy altered excitability. Targeting NF1, contrast, caused increased astrocytogenesis at expense neurogenesis, combined targeting three suppressors (PTEN, NF1 P53) resulted formation glioblastoma tumors. Our results demonstrate can produce unique models disruption tumors by mutation progenitors.