Neural Differentiation Is Inhibited through HIF1α/β-Catenin Signaling in Embryoid Bodies

Figure 5

Scheme indicating the possible role of HIF-1α/β-catenin in the regulation of neurogenesis in vitro. During spontaneous differentiation, HIF1α is stabilized in the increasing hypoxic environment of growing EBs; this protects β-catenin from degradation in the cytoplasm, which in turn increases the localization of active β-catenin in the nucleus, where β-catenin activates several genes involved in mesodermal differentiation while inhibiting neural differentiation. In the absence of HIF1α, β-catenin is degraded at a higher rate, which reduces its activity in the nucleus, and the cell is driven to premature neurogenesis (increased NeuroD1 and PAX6), probably through the downregulation of the Lef1 gene (see Discussion for more detailed information and references).