Abstract
A major unsolved question in cortical development is how proliferation, neurogenesis, regional growth, regional identity, and laminar fate specification are coordinated. Here we provide evidence, using loss-of-function and gain-of-function manipulations, that the COUP-TFI orphan nuclear receptor promotes ventral cortical fate, promotes cell cycle exit and neural differentiation, regulates the balance of early- and late-born neurons, and regulates the balanced production of different types of layer V cortical projection neurons. We suggest that COUP-TFI controls these processes by repressing Mapk/Erk, Akt, and beta-catenin signaling.
Highlights
The neocortex processes different types of sensory and higher order information in distinct areas located at particular anteroposterior and dorsoventral (D/V) tangential coordinates (Grove and Fukuchi-Shimogori 2003; Sur and Rubenstein 2005)
We measured the PP/cortical plate (CP) formation in D6/COUP-TFI-COUP-TFI KO cortex (D6) (Fig. 4G, measurements performed in boxes in 3A#--C #) and COUP-TFI--/-- (Fig. 4H, measurements performed in boxes in S3), and we found an initial outgrowth in D6 animals (Fig. 4G, red line), followed by a reduced CP thickness after E13.5, showing a decrease of neuron-generating progenitors
By assessing the effect of increased and decreased COUP-TFI dosage, we show that it contributes to 1) patterning D/V properties of the cortex, 2) promoting cell cycle exit and neural differentiation, 3) regulating the balance of early- and late-born cells, and 4) regulating the balance of different types of cortical projection neurons
Summary
The neocortex processes different types of sensory and higher order information in distinct areas located at particular anteroposterior and dorsoventral (D/V) tangential coordinates (Grove and Fukuchi-Shimogori 2003; Sur and Rubenstein 2005). The radial organization of the 6 neural layers within each area is similar, each area has important differences in features of its molecular, cellular, and connectivity signature (Rakic 1988; Monuki and Walsh 2001; Molyneaux et al 2007). Ongoing studies are aimed at elucidating the developmental mechanisms that generate neocortical areas (O’Leary and Nakagawa 2002; Grove and Fukuchi-Shimogori 2003; Sur and Rubenstein 2005). The molecular mechanisms that coordinate these processes are not known
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