Any way you splice it: FGF8 in development

A new paper in the January 15th issue of G&D provides the structural basis by which FGF8 splice isoforms (FGF8a and FGF8b) differ in their ability to pattern embryonic brain. FGF8b differs from FGF8a solely by the presence of 11 additional amino acids at its N-terminus.

However, only FGF8b can transform midbrain to cerebellum whereas FGF8a causes an overgrowth of midbrain. Dr. Moosa Mohammadi’s research team has solved the crystal structure of FGF8b in complex with the FGFR2c receptor, and shows that additional contacts between a single amino acid from the alternatively spliced region of FGF8b with the FGFR2c receptor account for the unique ability of FGF8b to transform midbrain to hindbrain during embryogenesis.

The structural and biochemical data not only provide novel insights into the molecular mechanisms of brain development, but also serves as a framework for examining the role of individual FGF8 isoforms in patterning and development of limb, eye, ear and lung. Moreover, this study is the first to demonstrate that differences in the strength of interaction of closely related growth factors with a common receptor can serve as a regulatory mechanism in cellular signaling.