ArticleProceedings of the National Academy of Sciences of the United States of America2014
Shp2/MAPK signaling controls goblet/paneth cell fate decisions in the intestine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 129 citations in OpenAlex.
- The anti-diarrheal role of iron in piglets: Regulation of colonic goblet cell function.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- A Rare T-Cell Factor 4 Lineage-negative Epithelial Stem Cell Supports Wound Repair and APC-deletion-induced Colon Tumorigenesis.bioRxiv : the preprint server for biology · 2026Article
- Intestinal stem and progenitor cells exhibit distinct adaptive responses to inflammatory stress in IBD.Stem cell research & therapy · 2025Article
- Targeting SHP2 to reverse immune evasion and resistance to anti-PD-1 therapy in non-small cell lung cancer.Cell communication and signaling : CCS · 2025Article
- Crosstalk between the circadian clock, intestinal stem cell niche, and epithelial cell fate decision.Genes & diseases · 2025Review
- PEDV infection downregulates goblet cell differentiation through activating the Notch pathway.Veterinary research · 2025Article
- The gut-heart axis: a correlation between Paneth cells' dysfunction, microbiome dysbiosis, and cardiovascular diseases.Cell communication and signaling : CCS · 2025Review
- Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell.Cell stem cell · 2025Article
- Impact of different feed intake levels on intestinal morphology and epithelial cell differentiation in piglets.Journal of animal science · 2025Article
- A tunable human intestinal organoid system achieves controlled balance between self-renewal and differentiation.Nature communications · 2025Article
- Chromatin remodelling in damaged intestinal crypts orchestrates redundant TGFβ and Hippo signalling to drive regeneration.Nature cell biology · 2024Article
- Review
- Cbl and Cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance.iScience · 2024Article
- Zinc glycine chelate ameliorates DSS-induced intestinal barrier dysfunction via attenuating TLR4/NF-κB pathway in meat ducks.Journal of animal science and biotechnology · 2024Article
- Mechanism of iron on the intestinal epithelium development in suckling piglets.Science China. Life sciences · 2023Article
- Organoid cell fate dynamics in space and time.Science advances · 2023Article
- Paneth cells as the cornerstones of intestinal and organismal health: a primer.EMBO molecular medicine · 2023Review
- Modeling Notch Activity and Lineage Decisions Using Intestinal Organoids.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Differentiated Epithelial Cells of the Gut.Methods in molecular biology (Clifton, N.J.) · 2023Article
- From birth to death: The hardworking life of Paneth cell in the small intestine.Frontiers in immunology · 2023Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the development of the mammalian intestine, Notch and Wnt/β-catenin signals control stem cell maintenance and their differentiation into absorptive and secretory cells. Mechanisms that regulate differentiation of progenitors into the three secretory lineages, goblet, paneth, or enteroendocrine cells, are not fully understood. Using conditional mutagenesis in mice, we observed that Shp2-mediated MAPK signaling determines the choice between paneth and goblet cell fates and also affects stem cells, which express the leucine-rich repeat-containing receptor 5 (Lgr5). Ablation of the tyrosine phosphatase Shp2 in the intestinal epithelium reduced MAPK signaling and led to a reduction of goblet cells while promoting paneth cell development. Conversely, conditional mitogen-activated protein kinase kinase 1 (Mek1) activation rescued the Shp2 phenotype, promoted goblet cell and inhibited paneth cell generation. The Shp2 mutation also expanded Lgr5+ stem cell niches, which could be restricted by activated Mek1 signaling. Changes of Lgr5+ stem cell quantities were accompanied by alterations of paneth cells, indicating that Shp2/MAPK signaling might affect stem cell niches directly or via paneth cells. Remarkably, inhibition of MAPK signaling in intestinal organoids and cultured cells changed the relative abundance of Tcf4 isoforms and by this, promoted Wnt/β-catenin activity. The data thus show that Shp2-mediated MAPK signaling controls the choice between goblet and paneth cell fates by regulating Wnt/β-catenin activity.
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