ArticleThe Journal of clinical investigation2012
Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 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
74 citing papers in PubMed, 98 citations in OpenAlex.
- Reactive oxygen species stimulate Paneth cell plasticity and diminish antimicrobial function.The EMBO journal · 2026Article
- CDC42 Regulatory Patterns Related To Inflammatory Bowel Disease and Hyperglycemia.Journal of bioinformatics and systems biology : Open access · 2025Article
- Salmonella engages CDC42 effector protein 1 for intracellular invasion.Journal of cellular physiology · 2024Article
- Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia.Genes & diseases · 2024Article
- Analysis of cell-specific transcriptional responses in human colon tissue using CIBERSORTx.Scientific reports · 2023Article
- Shaping infant development from the inside out: Bioactive factors in human milk.Seminars in perinatology · 2023Review
- Cellular shape reinforces niche to stem cell signaling in the small intestine.Science advances · 2022Article
- Article
- Cell clusters containing intestinal stem cells line, the zebrafish intestine intervillus pocket.iScience · 2022Article
- Impact of Epithelial Cell Shedding on Intestinal Homeostasis.International journal of molecular sciences · 2022Review
- Rab21 in enterocytes participates in intestinal epithelium maintenance.Molecular biology of the cell · 2022Article
- Article
- The role of cell division control protein 42 in tumor and non-tumor diseases: A systematic review.Journal of Cancer · 2022Review
- Colonic healing requires Wnt produced by epithelium as well as Tagln+ and Acta2+ stromal cells.Development (Cambridge, England) · 2022Article
- Role of Rho GTPases in stem cell regulation.Biochemical Society transactions · 2021Review
- Rab22a regulates the establishment of epithelial polarity.Small GTPases · 2021Article
- Review
- Tuba Activates Cdc42 during Neuronal Polarization Downstream of the Small GTPase Rab8a.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Review
- Elevating EGFR-MAPK program by a nonconventional Cdc42 enhances intestinal epithelial survival and regeneration.JCI insight · 2020Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The constant self renewal and differentiation of adult intestinal stem cells maintains a functional intestinal mucosa for a lifetime. However, the molecular mechanisms that regulate intestinal stem cell division and epithelial homeostasis are largely undefined. We report here that the small GTPases Cdc42 and Rab8a are critical regulators of these processes in mice. Conditional ablation of Cdc42 in the mouse intestinal epithelium resulted in the formation of large intracellular vacuolar structures containing microvilli (microvillus inclusion bodies) in epithelial enterocytes, a phenotype reminiscent of human microvillus inclusion disease (MVID), a devastating congenital intestinal disorder that results in severe nutrient deprivation. Further analysis revealed that Cdc42-deficient stem cells had cell division defects, reduced capacity for clonal expansion and differentiation into Paneth cells, and increased apoptosis. Cdc42 deficiency impaired Rab8a activation and its association with multiple effectors, and prevented trafficking of Rab8a vesicles to the midbody. This impeded cytokinesis, triggering crypt apoptosis and disrupting epithelial morphogenesis. Rab8a was also required for Cdc42-GTP activity in the intestinal epithelium, where continued cell division takes place. Furthermore, mice haploinsufficient for both Cdc42 and Rab8a in the intestine demonstrated abnormal crypt morphogenesis and epithelial transporter physiology, further supporting their functional interaction. These data suggest that defects of the stem cell niche can cause MVID. This hypothesis represents a conceptual departure from the conventional view of this disease, which has focused on the affected enterocytes, and suggests stem cell-based approaches could be beneficial to infants with this often lethal condition.
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.