Morphogen gradient reconstitution reveals Hedgehog pathway design principles
Year: 2018
Type: article
Abstract: 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 have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that 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 with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning.
Source: Science
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Howard Hughes Medical Institute, American Cancer Society, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Institute for Collaborative Biotechnologies
Awards: G1242324316, Bilateral NSF/BIO-BBSRC: The design logic of Hedgehog-based pattern formation., Spatio-Temporal Signaling Dynamics in Neuronal Cell Fate Decision and Patterning, Bottom-up reconstitution of BMP morphogenetic pattern formation, Spatio-Temporal Signaling Dynamics in Neuronal Cell Fate Decision and Patterning, G6594061099
OpenAlex ID: W2796439542