Inferring the structures of signaling motifs from paired dynamic traces of single cells
Fig 1
Signaling motifs determine how upstream signals are converted into downstream responses.
(A) The same upstream signal, X, can produce different downstream responses, Z, depending on the signaling motif. Positive feedback leads to rapid amplification of Z following a delay in its induction. An incoherent feedforward loop (IFFL) allows Z to adapt to changes in X by first activating then dampening the downstream response. Coupled positive and negative feedback can lead to oscillations of Z. Signaling motifs often involve an intermediate signaling factor, Y, that is necessary to achieve the appropriate downstream response. Ordinary differential equations for each signaling motif are provided in the S1 Text. (B) In response to a given stimulus, individual cells show heterogeneous signaling patterns. For many cellular signaling pathways, the variability of the upstream signal, X, is correlated with the downstream response, Z. (C) Hypothetical model for a common signaling motif that explains the correlation between upstream signaling and downstream responses. Differences in upstream signal are mapped onto the downstream response. Under this model, it may be possible to infer the underlying structure by observing many examples of the upstream and downstream signaling patterns.