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| Molecular mechanisms regulating olfactory bulb formation |
| Fumiaki Imamura, Claire Miller, Ayako Ito Penn State College of Medicine, Hershey, PA, United States |
The olfactory bulb (OB) evaginates from the anterior end of the telencephalic vesicle during brain development. However, the cellular and molecular mechanisms regulating OB formation are unique and different from those of the cerebral cortex. Indeed, OB dysplasia can occur without significant defects in the cerebral cortex, which results in congenital olfactory defects. For example, more than 90% of children with Kallmann syndrome are born with anosmia or hyposmia associated with the absence or dysplasia of the OBs. However, the molecular mechanisms regulating OB formation are largely unknown. In this study, we first investigated the role of FGF signaling in OB formation, since fgf8 and fgfr1 are causative genes of Kallmann syndrome. To locally inhibit FGF signaling, a dominant-negative form of FGFR1 was introduced into the anterior end of the telencephalon by in utero electroporation. We found that inhibition of FGFR1 signaling aberrantly promoted the neuronal differentiation of radial glial cells (RGCs) in the OB (OB RGCs), which resulted in OB hypoplasia, suggesting that FGF signaling regulates normal OB formation by controlling the development of RGCs. Furthermore, we found that inhibition of FGF signaling downregulated noggin expression in the OB. Since noggin is an antagonist of BMP receptors, we also examined the role of the BMP signal in OB formation. Interestingly, the overactivation of BMP signaling in OB RGCs resulted in OB hypoplasia. These results suggest that crosstalk between FGF and BMP signaling pathways in the OB RGCs is important for proper OB formation during development. I will present our research results and discuss how Dr. Gordon Shepherd’s research shaped the trajectory of my career. |