Regulation of transcription and cell identity by FGF/ERK signaling dynamics in embryonic stem cells

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The differentiation of specialized cell types from progenitor cells underlies both embryonic development and the maintenance of adult cycling tissues. Extracellular signaling factors play central roles in regulating cell differentiation by modulating transcription via intracellular signal transduction systems. How these signaling systems transmit quantitative information from the plasma membrane to the transcriptional machinery is still poorly understood. We address this question in the context of fibroblast growth factor (FGF) signaling through extracellular regulated kinase (ERK) in embryonic stem cells (ESCs). FGF/ERK signaling plays crucial roles during the earliest steps of ESC differentiation in vitro, mirroring the functions of this signaling system during early mammalian embryogenesis. We will exploit the accessibility of the ESC system for imaging approaches to elucidate the roles of both transcriptional and signaling dynamics for the faithful information transmission from the FGF receptor to the transcription of target genes. Specifically, we will test the hypothesis that dynamic activation patterns of ERK encode information about ligand abundance that can be decoded by the transcriptional machinery. By exploring the concept of dynamic encoding of FGF signals, our studies will impact our understanding of quantitative information transmission from the plasma membrane to the nucleus in general.