FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment

摘要: Pluripotent embryonic stem (ES) cells must select between alternative fates of self-replication and lineage commitment during continuous proliferation. Here, we delineate the role of autocrine production fibroblast growth factor 4 (Fgf4) associated activation Erk1/2 (Mapk3/1) signalling cascade. Fgf4 is major stimulus activating Erk in mouse ES cells. Interference with FGF or activity using chemical inhibitors genetic ablations does not impede propagation undifferentiated cells. Instead, such manipulations restrict ability to commit to differentiation. lacking treated receptor inhibitors resist neural mesodermal induction, are refractory BMP-induced non-neural differentiation. Lineage potential -null cells restored by provision protein. Thus, enables rather than antagonises differentiation BMP. The key downstream of Erk signalling revealed examination Erk2- null cells, which fail undergo either adherent culture, retain expression pluripotency markers Oct4, Nanog Rex1. These findings establish that stimulation an autoinductive stimulus for naive exit self-renewal programme. We propose cascade directs transition a state responsive to inductive cues germ layer segregation. Consideration signalling as primary trigger potentiates provides context for reconciling disparate views on contribution BMP pathways during specification vertebrate embryos.