The Level of the Transcription Factor Pax6 Is Essential for Controlling the Balance between Neural Stem Cell Self-Renewal and Neurogenesis

• DOI: 10.1371/journal.pgen.1000511
• Publication Date: 2009-06-11T22:06:59Z
• Authors: Stephen N. Sansom; Dean S. Griffiths; Andrea Faedo; Dirk-Jan Kleinjan; Youlin Ruan; James Smith; Veronica van Heyn...; John L. Rubenstein; Frederick J. Livesey
• Keywords: PAX6

Neural stem cell self-renewal, neurogenesis, and fate determination are processes that control the generation of specific classes neurons at correct place time. The transcription factor Pax6 is essential for neural proliferation, multipotency, neurogenesis in many regions central nervous system, including cerebral cortex. We used as an entry point to define cellular networks controlling self-renewal cells developing mouse identified genomic binding locations neocortical during normal development ascertained functional significance genes we found be regulated by Pax6, finding positively directly regulates cohorts promote basal progenitor genesis, neurogenesis. Notably, defined a core network regulating decision-making which interacts with three other regulators Neurog2, Ascl1, Hes1. Analyses biological function through phenotypic analyses gain- loss-of-function mutant cortices demonstrated Pax6-regulated operating highly dosage sensitive. Increasing levels drives system towards genesis increasing expression cohort determinants, key Eomes/Tbr2, thus expense self-renewal. Removing reduces cortical decreasing cycle regulators, resulting excess early find relative Hes1, Neurog2 determinants dynamic controls whether self-renew, generate neurons, or cells, mechanism has marked parallels transcriptional embryonic