The stratification of the cerebral cortex is one of the most prominent features of the mammalian brain. Neurons at different layers are born at different birth dates and exhibit distinct functions; these are largely subdivided into the upper (layers 2-4) and deep layers (layers 5 and 6). This cytoarchitecture provides a framework for cortical circuit formation; perceptive inputs are typically received by layer 4 neurons, and then processed, integrated in the upper layer neuronal network, and subsequently transduced to the deep layer neurons that further convey outputs into other brain regions. While the upper layers of the cerebral cortex expanded rapidly during mammalian evolution, little is known about the mechanisms controlling the proportion of the upper layers to the deep layers.
Recently, in the course of our study of the self-renewal of mouse radial glia, we observed that FGF18 (1), which is transiently expressed in deep layer neurons (2), controls the self-renewal potential of radial glia. FGF18 in the mouse dorsal cortex is mainly expressed in the deep layers and the subplate during a narrow time window of E13-E16. In FGF18 mutants, a 20-30% reduction of radial glia and an increase in intermediate progenitors was observed at E14.5. This conversion in progenitors results in a reduction in the number of late-born neurons (layer 2 and layer 3) by 20-30%, while the early-born neuronal populations of deep layers were not significantly affected. Thus, FGF18 regulates the proportion of the upper layer neurons relative to the deep layer neurons by promoting the self-renewal of the progenitors that are producing the upper-layer neurons. We are currently examining whether FGF18 signaling is, at least in part, mediated by the basal process of radial glia. Taken together, our study suggests the existence of a novel positive feedback mechanism from neurons to progenitors to modulate the proportion of cortical layers.

1) Ohbayashi et al. (2002). Genes Dev 16, 870-879.
2) Hasegawa et al. (2004) J Neurosci 24, 8711-8719.