Morphogen gradient reconstitution reveals Hedgehog pathway design principles

Author:

Li Pulin1ORCID,Markson Joseph S.1ORCID,Wang Sheng1ORCID,Chen Siheng1ORCID,Vachharajani Vipul1,Elowitz Michael B.12ORCID

Affiliation:

1. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

2. Howard Hughes Medical Institute and Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.

Abstract

How to build a better morphogen gradient To translate insights in developmental biology into medical applications, techniques are needed to ensure correct cell localization. Morphogen gradients allow precise and highly reproducible pattern formation during development. Through in vitro experiments and modeling, Li et al. tested the effects of unusual properties of Hedgehog (HH) signaling. The HH morphogen's receptor, Patched (PTCH), sends an inhibitory signal when no ligand is bound, which is relieved by ligand binding. PTCH also regulates spatial distribution of the signal by sequestering the HH ligand. Furthermore, signaling through the receptor promotes synthesis of more inhibitory receptor. These characteristics help speed gradient formation and explain the robustness of the system to changes in the rate of morphogen production. Science , this issue p. 543

Funder

National Science Foundation

National Institutes of Health

Howard Hughes Medical Institute

American Cancer Society

National Institute of Child Health and Human Development

Institute for Collaborative Biotechnologies

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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