12-P017 Fgfr3 regulates development of the caudal cerebral cortex

Structural changes caused by altered Fibroblast Growth Factor (FGF) signaling during embryonic development have been shown to influence cortical function and animal behavior. FGFs are known to control patterning and neurogenesis, the initial two key events that define forebrain structures. We hypothesized that one of the four high-affinity FGF receptors, Fgfr3, may regulate rostrocaudal forebrain patterning and neurogenesis, and that this function may be shared with other FGFR subtypes through co-regulation of downstream pathways. Here we investigated the phenotype of the cerebral cortex and hippocampus in Fgfr3 knockout mice in embryonic and early postnatal stages. We found that Fgfr3 homozygous knockout mice (Fgfr3 / ) rarely survived beyond birth on a C57/Bl6 background. However, the production efficiency improved upon backcrossing onto a CD1 background. A reduction in the brain weight and size was detected in Fgfr3 / in comparison to +/ and +/+ littermate controls as early as E16.5, and more prominently at E18.5/P0.5. The overall structure appeared largely normal in the Fgfr3 / cortex and hippocampus at postnatal day 7.5. However, the volume of Fgfr3 / was reduced compared to controls by 26.7% and 22.5% in the cortex and hippocampus, respectively (n = 3). This reduction is largely comparable to that observed in mouse models with Fgfr1 deletion. Finally, diffusion magnetic resonance imaging and tractography revealed a decrease in caudal cortical tracts crossing the midline via the anterior commissure. All together, these results suggest that Fgfr3 is important for formation of caudal regions of the cerebral cortex.