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.
Abstract

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