“…While we did not detect signs of genomic instability leading to p53 activation, DNA damage pathways can become activated in the absence of Lsh 69 , and may result in increased genomic instability and a decrease in survival. Alternatively, our RNA-seq analysis found several significantly de-regulated genes which may contribute to decreased growth/survival of Lsh−/− NSPCs; for example, the IPW gene, a long noncoding RNA which is overexpressed in the Prader-Willi syndrome, a genetic condition with multiple deficiencies, including cognitive and behavioral disturbances 71 , the cell cycle regulator Plk1, Cdca3 and the centromeric protein Cenpf, which can modulate proliferation and neurodevelopmental associated functions 72 – 74 , the transcription factors Dlx1 and Dlx2, which play a role in brain and craniofacial development 75 , and the Aspm genes that control brain size 76 . Thus several factors that are abnormally expressed in Lsh mutant NSPCs may potentially synergize and contribute to impaired neural stem cell renewal.…”