Evidence map›Paper›PMID 26674309›Full record

ArticleDevelopment (Cambridge, England)2016

Sonic hedgehog controls enteric nervous system development by patterning the extracellular matrix.

Nandor Nagy, Csilla Barad, Hannah K Graham, Ryo Hotta, Lily S Cheng, Nora Fejszak, Allan M Goldstein

Abstract read
In one paragraph

Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
5.6field-weighted citation impact, top 4% of its field
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

38 citing papers in PubMed, 58 citations in OpenAlex.

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  10. Hirschsprung disease.Nature reviews. Disease primers · 2023
    Review
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  14. Review
  15. Article
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  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Nandor NagyDepartment of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA Department of Human Morphology and Developmental Biology, Faculty of Medicine, Semmelweis University, Budapest 1094, Hungary nagy.nandor@med.semmelweis-univ.hu.
Csilla BaradDepartment of Human Morphology and Developmental Biology, Faculty of Medicine, Semmelweis University, Budapest 1094, Hungary.
Hannah K GrahamDepartment of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Ryo HottaDepartment of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Lily S ChengDepartment of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Nora FejszakDepartment of Human Morphology and Developmental Biology, Faculty of Medicine, Semmelweis University, Budapest 1094, Hungary.
Allan M GoldsteinDepartment of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Harvard University · USSemmelweis University · HUMassachusetts General Hospital · US

Funding

Gdnf and endothelin-3 regulate colorectal enteric nervous system developmentR01DK080914 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI GOLDSTEIN, ALLAN M · 2009 to 2013
$2.0M
NIDDK NIH HHS R01 DK080914NIDDK NIH HHS R01DK080914
6 · The paper itself

Abstract

The enteric nervous system (ENS) develops from neural crest cells that migrate along the intestine, differentiate into neurons and glia, and pattern into two plexuses within the gut wall. Inductive interactions between epithelium and mesenchyme regulate gut development, but the influence of these interactions on ENS development is unknown. Epithelial-mesenchymal recombinations were constructed using avian hindgut mesenchyme and non-intestinal epithelium from the bursa of Fabricius. These recombinations led to abnormally large and ectopically positioned ganglia. We hypothesized that sonic hedgehog (Shh), a secreted intestinal epithelial protein not expressed in the bursa, mediates this effect. Inhibition of Shh signaling, by addition of cyclopamine or a function-blocking antibody, resulted in large, ectopic ganglia adjacent to the epithelium. Shh overexpression, achieved in ovo using Shh-encoding retrovirus and in organ culture using recombinant protein, led to intestinal aganglionosis. Shh strongly induced the expression of versican and collagen type IX, whereas cyclopamine reduced expression of these chondroitin sulfate proteoglycans that are known to be inhibitory to neural crest cell migration. Shh also inhibited enteric neural crest-derived cell (ENCC) proliferation, promoted neuronal differentiation, and reduced expression of Gdnf, a key regulator of ENS formation. Ptc1 and Ptc2 were not expressed by ENCCs, and migration of isolated ENCCs was not inhibited by Shh protein. These results suggest that epithelial-derived Shh acts indirectly on the developing ENS by regulating the composition of the intestinal microenvironment.

Indexed as

AnimalsApoptosisCell MovementChickensEnteric Nervous SystemExtracellular MatrixHedgehog ProteinsImmunohistochemistryIn Situ HybridizationMicePatched-1 ReceptorPatched ReceptorsQuailReceptors, Cell SurfaceSignal TransductionHedgehog ProteinsPatched-1 ReceptorPatched ReceptorsPTCH1 protein, humanPtch1 protein, mouseReceptors, Cell SurfaceChickEnteric nervous systemEnteric neural crest cellsEpitheliumExtracellular matrixHirschsprung diseaseMousePatchedPtchQuailSonic hedgehog

Identifiers

PMID26674309
PMCPMC4725345
OpenAlexW2248228111

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.