The Role of Fibroblast Growth Factor Receptors in the Morphogenesis and Maturation of the Neocortex

Fibroblast growth factors (Fgf) establish the primary structure of the cerebral cortex by controlling the self-renewal of radial glial stem cells and the differentiation of projection neurons from embryonic radial glial precursors. Our studies have shown that Fgf signaling acts upstream of Notch to regulate the surface expansion of the cerebral cortex and the hippocampus. Reduction of all Fgf receptor signaling in early neurogenesis depletes the stem cell pool resulting in premature ending of neurogenesis and decreased cortical surface area (Rash et al, 2011). Single Fgf receptors play more specific roles, Fgfr2 contributing to volume expansion of the prefrontal cortex (Stevens et al, 2010) and Fgfr1 of the hippocampus (Ohkubo et al, 2004) and cortical midline (Smith et al, 2006). We are currently studying dose-specific Fgf effects in the development of neocortical size, structure and molecular profile.

Fgf ligands also play roles in different epochs of postnatal and adult life. Induced loss of Fgf signaling only in postnatal astrocytes generates impairments in locomotor activity and learning that correlate with deficit in specific cell populations in the postnatal brain (Stevens et al, 2012). Fgf also function in astroglia to influence maturation of inhibitory interneurons during postnatal cortical development of the cerebral cortex (Smith et al, 2014).