Evidence map›Paper›PMID 29622726›Full record

ArticleScience (New York, N.Y.)2018

Morphogen gradient reconstitution reveals Hedgehog pathway design principles.

Pulin Li, Joseph S Markson, Sheng Wang, Siheng Chen, Vipul Vachharajani, Michael B Elowitz

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Heparan sulfate is essential for Drosophila FGF export.bioRxiv : the preprint server for biology · 2026
    Article
  6. Systemic Sonic Hedgehog Signaling Links Intestinal Nutrient Sensing With Sex-Specific Type 2 Diabetes Progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  7. Article
  8. Review
  9. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Pulin LiDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.ORCID 0000-0002-8525-4936
Joseph S MarksonDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.ORCID 0000-0002-3167-3887
Sheng WangDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.ORCID 0000-0002-4070-7313
Siheng ChenDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.ORCID 0000-0002-5494-0853
Vipul VachharajaniDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Michael B ElowitzDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. melowitz@caltech.edu.ORCID 0000-0002-1221-0967

Funding

Spatio-Temporal Signaling Dynamics in Neuronal Cell Fate Decision and PatterningR00HD087532 · NICHD · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI LI, PULIN · 2019 to 2021
$736k
Spatio-Temporal Signaling Dynamics in Neuronal Cell Fate Decision and PatterningK99HD087532 · NICHD · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LI, PULIN · 2016 to 2017
$200k
Bottom-up reconstitution of BMP morphogenetic pattern formationF32AR067103 · NIAMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI MARKSON, JOSEPH SCOTT · 2014 to 2016
$175k
NIAMS NIH HHS F32 AR067103NICHD NIH HHS K99 HD087532NICHD NIH HHS R00 HD087532
6 · The paper itself

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.

Indexed as

AnimalsBody PatterningFeedback, PhysiologicalHedgehog ProteinsMetabolic Networks and PathwaysMiceModels, BiologicalNIH 3T3 CellsPatched-1 ReceptorSequence DeletionSignal TransductionHedgehog ProteinsPatched-1 Receptor

Identifiers

PMID29622726
PMCPMC6516753

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.