Trial reportThe Journal of clinical investigation2015
A collagen VI-dependent pathogenic mechanism for Hirschsprung's disease.
Trial report in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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.
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.
Who cites it
52 citing papers in PubMed, 95 citations in OpenAlex.
- Subtypes of Enteric Neurons in Hirschsprung Disease: A Comparison of Fully Ganglionic and Transitional Zone.Neurogastroenterology and motility · 2026Article
- Article
- Oxidative Stress and Antioxidant Defense Mechanisms inAntioxidants (Basel, Switzerland) · 2026Article
- Retinol dehydrogenase 10-mediated retinoic acid signaling regulates the neural crest cell microenvironment during enteric nervous system formation.Human molecular genetics · 2026Article
- Perlecan, CollagenXVIII, and Agrin Expression in Normo-, Hypo-, and Aganglionic Segments in Hirschsprung's Disease.Neurogastroenterology and motility · 2026Article
- Tracing the enteric neural crest cell pathway from origin to colonization: insights into Hirschsprung's disease.Molecular biology reports · 2025Review
- Hirschprung's Disease and Thoracic Limb Amputation by Amniotic Bands in a Patient With Down Syndrome: A Case Report.Clinical case reports · 2025Article
- Brain-Specific Gata4 Downregulation in Greywick Female Mice Models the Metabolic Subtype of Polycystic Ovary Syndrome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The Suggested Relationships Between Common GI Symptoms and Joint Hypermobility, POTS, and MCAS.Gastroenterology & hepatology · 2024Article
- Efficient enzyme-free method to assess the development and maturation of the innate and adaptive immune systems in the mouse colon.Scientific reports · 2024Article
- Agrin Inhibition in Enteric Neural Stem Cells Enhances Their Migration Following Colonic Transplantation.Stem cells translational medicine · 2024Article
- Hirschsprung disease.Nature reviews. Disease primers · 2023Review
- mRNA sequencing provides new insights into the pathogenesis of Hirschsprung's disease in mice.Pediatric surgery international · 2023Article
- Harnessing the Power of Enteric Glial Cells' Plasticity and Multipotency for Advancing Regenerative Medicine.International journal of molecular sciences · 2023Review
- Visualizing enteric nervous system activity through dye-free dynamic full-field optical coherence tomography.Communications biology · 2023Article
- Hirschsprung's disease: key microRNAs and target genes.Pediatric research · 2022Article
- CHARGE syndrome-associated proteins FAM172A and CHD7 influence male sex determination and differentiation through transcriptional and alternative splicing mechanisms.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Overexpression of the Hsa21 Transcription Factor RUNX1 Modulates the Extracellular Matrix in Trisomy 21 Cells.Frontiers in genetics · 2022Article
- Genetic Background Influences Severity of Colonic Aganglionosis and Response to GDNF Enemas in theInternational journal of molecular sciences · 2021Article
- Roles of Enteric Neural Stem Cell Niche and Enteric Nervous System Development in Hirschsprung Disease.International journal of molecular sciences · 2021Review
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Hirschsprung's disease (HSCR) is a severe congenital anomaly of the enteric nervous system (ENS) characterized by functional intestinal obstruction due to a lack of intrinsic innervation in the distal bowel. Distal innervation deficiency results from incomplete colonization of the bowel by enteric neural crest cells (eNCCs), the ENS precursors. Here, we report the generation of a mouse model for HSCR--named Holstein--that contains an untargeted transgenic insertion upstream of the collagen-6α4 (Col6a4) gene. This insertion induces eNCC-specific upregulation of Col6a4 expression that increases total collagen VI protein levels in the extracellular matrix (ECM) surrounding both the developing and the postnatal ENS. Increased collagen VI levels during development mainly result in slower migration of eNCCs. This appears to be due to the fact that collagen VI is a poor substratum for supporting eNCC migration and can even interfere with the migration-promoting effects of fibronectin. Importantly, for a majority of patients in a HSCR cohort, the myenteric ganglia from the ganglionated region are also specifically surrounded by abundant collagen VI microfibrils, an outcome accentuated by Down syndrome. Collectively, our data thus unveil a clinically relevant pathogenic mechanism for HSCR that involves cell-autonomous changes in ECM composition surrounding eNCCs. Moreover, as COL6A1 and COL6A2 are on human Chr.21q, this mechanism is highly relevant to the predisposition of patients with Down syndrome to HSCR.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.