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Active β-Catenin Signaling in the Small Intestine of Humans During Infancy
Zenab M Dudhwala1, Paul A Drew2,3, Gordon S Howarth4,5
1Gastroenterology Research Laboratory, Discipline of Medicine, University of Adelaide, and Basil Hetzel Institute for Translational Health Research, 37a Woodville Road, Woodville South, SA, 5011, Australia. zenab.dudhwala@adelaide.edu.au.
Insights
Wnt-β-catenin signaling drives intestinal stem cell activity and crypt fission in infants. This pathway is crucial for postnatal growth and development in the infant gut.
Area of Science:
- Gastroenterology
- Developmental Biology
- Molecular Biology
Background:
- Wnt-β-catenin signaling is vital for intestinal stem cell (ISC) homeostasis.
- This pathway is implicated in promoting intestinal crypt fission in mice.
Purpose of the Study:
- To investigate the role and activity of Wnt-β-catenin signaling in the intestinal crypts of human infants.
- To compare Wnt-β-catenin signaling activity between infant and adult intestinal tissues.
Main Methods:
- Duodenal biopsies were collected from infants (0.3-2 years) and adults (34-71 years).
- Immunoperoxidase staining assessed cytoplasmic/nuclear β-catenin, nuclear c-Myc, and cytoplasmic Axin-2 expression at the crypt base.
- Quantitative analysis using cumulative signal analysis and Student's t-test compared infant and adult tissues.
Main Results:
- Infant intestinal crypts exhibited significantly higher fission rates (16%) compared to adults (0.7%).
- Wnt-β-catenin signaling markers (β-catenin, Axin-2) were significantly elevated in infants.
- c-Myc expression was observed in the transit amplifying zone and crypt base columnar cells, but not Paneth cells.
Conclusions:
- Wnt-β-catenin signaling is active in intestinal stem cells of human infants, potentially driving increased crypt fission.
- This signaling pathway likely contributes to postnatal intestinal growth in concert with other pathways.
Background:
Wnt-β-catenin signaling is essential for homeostasis of intestinal stem cells in mice and is thought to promote intestinal crypt fission.
Aims:
The aim of this study was to investigate Wnt-β-catenin signaling in intestinal crypts of human infants.
Methods:
Duodenal biopsies from nine infants (mean, range 0.9 years, 0.3-2 years) and 11 adults (mean, range 43 years, 34-71 years) were collected endoscopically. Active β-catenin signaling was assessed by cytoplasmic and nuclear β-catenin, nuclear c-Myc, and cytoplasmic Axin-2 expression in the base of crypts. Tissues were stained by an immunoperoxidase staining technique and quantified as pixel energy using cumulative signal analysis. Data were expressed as mean ± SD and significance assessed by Student's t test.
Results:
Crypt fission was significantly higher in infants compared to adults (16 ± 8.6% versus 0.7 ± 0.6%, respectively, p < 0.0001). Expression of cytoplasmic and nuclear β-catenin was 1.8-fold (p < 0.0001) and 2.9-fold (p < 0.0001) higher in infants, respectively, while cytoplasmic Axin-2 was 3.1-fold (p < 0.0001) increased in infants. c-Myc expression was not significantly different between infants and adults. Expression was absent in Paneth cells but present in the transit amplifying zone of crypts. Crypt base columnar cells, which were intercalated between Paneth cells, expressed c-Myc.
Conclusions:
Wnt-β-catenin signaling was active in crypt base columnar cells (i.e., intestinal stem cells) in human infants. This signaling could promote crypt fission during infancy. Wnt-β-catenin signaling likely acts in concert with other pathways to promote postnatal growth.
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