T-cell factor 4 (Tcf7l2) maintains proliferative compartments in zebrafish intestine

Vanesa Muncan, Ana Faro, Anna Pavlina G. Haramis, Adam F.L. Hurlstone, Erno Wienholds, Johan van Es, Jeroen Korving, Harry Begthel, Danica Zivkovic, Hans Clevers

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


Previous studies have shown that Wnt signals, relayed through β-catenin and T-cell factor 4 (Tcf4), are essential for the induction and maintenance of crypts in mice. We have now generated a tcf4 (tcf7l2) mutant zebrafish by reverse genetics. We first observe a phenotypic defect at 4 weeks post-fertilization (wpf), leading to death at about 6 wpf. The phenotype comprises a loss of proliferation at the base of the intestinal folds of the middle and distal parts of the intestine. The proximal intestine represents an independent compartment, as it expresses sox2 in the epithelium and barx1 in the surrounding mesenchyme, which are early stomach markers in higher vertebrates. Zebrafish are functionally stomach-less, but the proximal intestine might share its ontogeny with the mammalian stomach. Rare adult homozygous tcf4-/- 'escapers' show proliferation defects in the gut epithelium, but have no other obvious abnormalities. This study underscores the involvement of Tcf4 in maintaining proliferative self-renewal in the intestine throughout life.

Original languageEnglish
Pages (from-to)966-973
Number of pages8
JournalEMBO Reports
Issue number10
Publication statusPublished - Oct 2007
Externally publishedYes


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