Outstanding questions in developmental ERK signaling

The extracellular signal-regulated kinase (ERK) pathway leads to activation of the effector molecule ERK, which controls downstream responses by phosphorylating a variety of substrates, including transcription factors. Crucial insights into the regulation and function of this pathway came from studying embryos in which specific phenotypes arise from aberrant ERK activation. Despite decades of research, several important questions remain to be addressed for deeper understanding of this highly conserved signaling system and its function. Answering these questions will require quantifying the first steps of pathway activation, elucidating the mechanisms of transcriptional interpretation and measuring the quantitative limits of ERK signaling within which the system must operate to avoid developmental defects.