| Two notable innovations found in the mammalian cortex, but not the cortical structures of lower vertebrates, are a second proliferative population in the germinal subventricular zone and a six-layered cortical structure. Expansion of the cortical lamina and the subventricular zone allow for an increase in the size and complexity of cerebral cortex, yet many aspects of their regulation are unknown. Here we show that beta-catenin signaling influences both of these processes. In the developing murine cortex, beta-catenin signaling is expressed in both temporal and spatial gradients. The intensity of beta-catenin signaling in the ventricular zone regulates the production of distinct classes of cortical projection neurons. The deep layer neurons are produced early in neurogenesis, when beta-catenin signaling is high, while upper layer neurons are produced later when beta-catenin signaling has diminished. Forced expression of stabilized beta-catenin in progenitors leads to increased deep layer neuron production. Blocking beta-catenin signaling with dominant negative TCF4 causes increased upper layer neuron production. Beta-catenin signaling also represses intermediate progenitor production. Regions of the cortex with high levels of beta-catenin signaling have few intermediate progenitors, while areas with low signaling have increased intermediate progenitor population. Conditional loss of beta-catenin function in the cortex expands the intermediate progenitor population. Persistent expression of stabilized beta-catenin represses intermediate progenitor cell fate. Thus, beta-catenin signaling gradations create progenitor cell and neuronal diversity in the cerebral cortex. |
