Signaling dynamics and embryonic development

During embryonic development, signaling molecules convey positional information within the embryo and direct cells to adopt particular fates. A crucial question is how do the receiving cells of the embryo interpret these signals? While most work on this issue has focused on the biochemical and genetic dissection of the molecular circuitry of signal transduction, understanding signaling as a dynamic process is crucial to understanding development. During development, the timing and duration of signaling can play an important role in determining cell fate. The TGF-β pathway plays a crucial role during the development of organisms from fly to human and mediates events such as mesoderm induction and DV patterning in vertebrates. In a recent study, we focused on unraveling the dynamics of TGF-b signaling in two developmentally relevant contexts, the myoblastic C2C12 cell line and the early Xenopus embryo. Activation of TGF-b receptors by ligand binding leads to the phosphorylation of receptor-regulated Smads (R-Smads), binding of R-Smads to Smad4, translocation of this complex to nucleus and transcriptional activation. Understanding the dynamics of a signaling pathway is equivalent to answering the question: if a cell is exposed to ligand with some particular dynamics, what are the resulting dynamics of signaling activity in that cell? In our study, we focused on the simplest possible situation: cells were exposed to a step increase in ligand concentration, and we monitored signaling activity as a function of time. This situation presents two possibilities (Fig. 1). In the simplest, the output tracks the ligand so that under sustained stimulation, the output is similarly sustained. An alternative is known as an adaptive response; that is, the cells respond to the change in Signaling dynamics and embryonic development