Autocrine- and paracrine-signaling modes play reciprocal roles in robust cell-cell communication.

The figure shows the effects of perturbing autocrine- and paracrine-signaling modes in theoretical mutant (TM) systems. [A] The TM-APM (inhibition of autocrine, paracrine, and membrane-exchange signaling) represents the loss-of-function phenotype of experimental FGF/ERK pathway mutants. [B, C] The complementary TM-A and TM-PM portray the importance of individual feedback modes (paracrine plus membrane exchange and autocrine signaling only, respectively; see also inset text). Solid lines represent mean and standard deviation values (μ and σ) for a given TM; dashed lines represent μ and σ for the inferred-theoretical wild-type (ITWT). [D] Cell-lineage allocation at the 48 h time point. All TMs are compared against the (ITWT). For all compared systems, statistics were calculated from 1000 independent simulation runs. Colors represent different cell fates: UND (olive); EPI (blue); PRE (orange).