CPM Seminar

Signaling dynamics and embryonic patterning

Aryeh Warmflash

Rockefeller University

During embryonic development, signaling pathways convey positional information in order to pattern the embryo. Although the timing of signaling exerts an important influence on patterning, the dynamical properties of developmental signaling pathways remain largely unexplored. The TGF-beta pathway plays a vital role in embryonic patterning and has been shown to act as a morphogen inducing cell fate in a concentration-dependent manner. We used integrated automated microfludic cell-culture and time-lapse microscopy to probe the dynamics of the signaling pathway under a variety of time courses of ligand stimulation that mimic those seen during embryonic development. We show that the pathway responds transiently and adaptively to a step in ligand stimulation and as a consequence of this adaptation: 1) pathway throughput is maximized by pulsatile stimulation and 2) the response to increasing ligand concentration depends strongly on the rate at which the ligand is presented. Mathematical modeling suggests that in an embryonic context, an adaptive pathway can extract positional information as ligand spreads dynamically from a source thereby providing an alternative to the static morphogen model. Thus, the rate of ligand presentation may be an important instructive signal for patterning.