ArticleDevelopment (Cambridge, England)2020
RET overactivation leads to concurrent Hirschsprung disease and intestinal ganglioneuromas.
Article in Development (Cambridge, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Full thickness three-dimensional mapping of neuronal populations within the avian enteric nervous system.Poultry science · 2026Article
- Time-resolved morphological and transcriptomic characterization of early enteric neuron subtype emergence in chick.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- miR-146b-5p Regulates the Enteric Nervous System Development in Hirschsprung Disease via Targeting RET Pathway.Biochemical genetics · 2025Article
- Cecal growth factors promote enteric neurosphere formation and hindgut colonization in the avian model.Frontiers in cell and developmental biology · 2025Article
- Three distinct classes of myenteric ganglia in mice and humans: insights from quantitative analyses.PeerJ · 2025Article
- Cancer Predisposition Syndromes and Thyroid Cancer: Keys for a Short Two-Way Street.Biomedicines · 2023Review
- CXCR4 and CXCL12 signaling regulates the development of extrinsic innervation to the colorectum.Development (Cambridge, England) · 2023Article
- A distinct transcriptome characterizes neural crest-derived cells at the migratory wavefront during enteric nervous system development.Development (Cambridge, England) · 2023Article
- A New Transgenic Tool to Study the Ret Signaling Pathway in the Enteric Nervous System.International journal of molecular sciences · 2022Article
- Intrauterine exposure to oxidative stress induces caspase-1-dependent enteric nerve cell pyroptosis.Pediatric surgery international · 2022Article
- Resection of Bilateral Symmetrical Multiple Level Cervical Ganglioneuroma in a 43-Year-Old Man, a Probable Case of Neurofibromatosis Type-1: Report of a Case and Review of Literature.Case reports in surgery · 2022Article
- Association of rs2435357 and rs2506030 polymorphisms inFrontiers in pediatrics · 2022Review
- Investigating natural compounds against oncogenic RET tyrosine kinase using pharmacoinformatic approaches for cancer therapeutics.RSC advances · 2021Article
- A Case Series Study of Solitary Mucosal Neuroma-Rare Cases of Benign Peripheral Neurogenic Tumours.Clinical pathology (Thousand Oaks, Ventura County, Calif.)Article
- Article
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Authors and funding
8 authors.
Funding
Abstract
Appropriately balanced RET signaling is of crucial importance during embryonic neural crest cell migration, proliferation and differentiation. RET deficiency, for example, leads to intestinal aganglionosis (Hirschsprung disease), whereas overactive RET can lead to multiple endocrine neoplasia (MEN) syndromes. Some RET mutations are associated with both intestinal aganglionosis and MEN-associated tumors. This seemingly paradoxical occurrence has led to speculation of a 'Janus mutation' in RET that causes overactivation or impairment of RET activity depending on the cellular context. Using an intestinal catenary culture system to test the effects of GDNF-mediated RET activation, we demonstrate the concurrent development of distal colonic aganglionosis and intestinal ganglioneuromas. Interestingly, the tumors induced by GDNF stimulation contain enteric neuronal progenitors capable of reconstituting an enteric nervous system when transplanted into a normal developmental environment. These results suggest that a Janus mutation may not be required to explain co-existing Hirschsprung disease and MEN-associated tumors, but rather that RET overstimulation alone is enough to cause both phenotypes. The results also suggest that reprogramming tumor cells toward non-pathological fates may represent a possible therapeutic avenue for MEN-associated neoplasms.
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