T-cell factor 4 (Tcf7l2) maintains proliferative compartments in zebrafish intestine.
Previous studies have shown that Wnt signals, relayed through beta-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.
Muncan
Vanesa
V
Netherlands Institute for Developmental Biology, Center for Biomedical Research, Hubrecht Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Faro
Ana
A
Haramis
Anna-Pavlina G
AP
Hurlstone
Adam F L
AF
Wienholds
Erno
E
van Es
Johan
J
Korving
Jeroen
J
Begthel
Harry
H
Zivkovic
Danica
D
Clevers
Hans
H
D000818:Animals; D049109:Cell Proliferation; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008297:Male; D009154:Mutation; D010641:Phenotype; D013997:Time Factors; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology