Understanding the robustness of Nodal signalling in mesendodermal patterning

Activator-inhibitor pairs underpin many developmental processes. Various roles of such motifs have been proposed, including to form Turing patterns, buffer fluctuations, or restrict spatiotemporal signalling extent. Mesendodermal induction is regulated through the activator-inhibitor pair formed by Nodal and Lefty proteins. Recent experiments suggest that mesendodermal patterning in zebrafish is "functional but fragile" without inhibitory feedback: is the role of this activator-inhibitor motif to buffer against environmental variability? Intriguingly, the Nodal signalling network resembles "antithetic integral feedback", which achieves robust control of single-cell averages. In this talk I will discuss the robustness of signalling gradients in spatially extended models of integral feedback. Our preliminary results suggest unadulterated antithetic integral feedback achieves poor regulation of signaling gradients when distributed across cellular compartments. However, we find that additional details of Nodal signalling may rectify spatially extended integral feedback, leading to improved robustness of signalling gradients.