Analysis of expression and function of FGF-MAPK signaling components in the hindbrain reveals a central role for FGF3 in the regulation of Krox20, mediated by Pea3

Abstract

The development of the vertebrate hindbrain requires multiple coordinated signals which act via several pathways. One such signal is Fibroblast Growth Factor (FGF), which is necessary for the patterning of a major transcription factor in the hindbrain, Krox20. However, in the chick, it is still not known which specific FGF ligand is responsible for the regulation of Krox20 and how the signal is dispatched. The most characterized signaling pathway which FGF acts through in the nervous system is the MAPK/Erk1/2 pathway. Nevertheless, a detailed analysis of the hindbrain distribution of various components of this pathway has not been fully described. In this study we present a comprehensive atlas of the FGF ligands, receptors and members of the MAPK/Erk1/2 signaling components in subsequent stages of avian hindbrain development. Moreover, we show that FGF is a major signaling pathway that contributes to the activation of ERK1/2 and expression of the downstream targets Pea3 and Erm. Central to this study, we provide multiple evidence that FGF3 is required for the upregulation of Pea3 that in turn is necessary for Krox20 distribution in rhombomeres 3 and 5. These results show for the first time that Pea3 mediates the FGF3 signal to regulate the hindbrain expression of Krox20.