Morphogen gradient reconstitution reveals Hedgehog pathway design principles

In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision remain unclear. Here, combining cell-based in vitro gradient reconstitution, genetic re-wiring, and mathematical modeling, we systematically analyzed the unique architectural features of the Sonic Hedgehog pathway. The combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared to alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes, and to compare the patterning behaviors of alternative, re-wired, pathway architectures offers a powerful way to understand and engineer multicellular patterning.

Pulin Li, Joseph S. Markson, Sheng Wang, Siheng Chen, Vipul Vachharajani and Michael B. Elowitz
Science
Volume: 360
Number: 6388
Pages: 543-548
Date: April, 2018
ICB Affiliated Authors: Michael B Elowitz