Nature Genetics
19, 379 - 383 (1998)
doi:10.1038/1270
Depletion of epithelial stem-cell compartments in the small intestine
of mice lacking Tcf-4Vladimir Korinek1, 2, Nick Barker1, Petra Moerer1, Elly van Donselaar3, Gerwin Huls1, Peter J. Peters3
& Hans Clevers11
Department of Immunology, University Hospital, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. 2
Present address: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Praha 4, Czech Republic. 3
Department of Cell Biology, University Hospital, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Correspondence should be addressed to Hans Clevers (H.Clevers@lab.azu.nl)Mutations of the genes encoding APC or  -catenin in colon carcinoma
induce the constitutive formation of nuclear -catenin/Tcf-4 complexes,
resulting in activated transcription of Tcf target genes1,
2.
To study the physiological role of Tcf-4 (which is encoded by the Tcf7l2
gene), we disrupted Tcf7l2 by homologous recombination. Tcf7l2
-/-mice die shortly after birth. A single histopathological abnormality
was observed. An apparently normal transition of intestinal endoderm into
epithelium occurred at approximately embryonic day (E) 14.5. However, no proliferative
compartments were maintained in the prospective crypt regions between the
villi. As a consequence, the neonatal epithelium was composed entirely of
differentiated, non-dividing villus cells. We conclude that the genetic program
controlled by Tcf-4 maintains the crypt stem cells of the small intestine.
The constitutive activity of Tcf-4 in APC-deficient human epithelial cells
may contribute to their malignant transformation by maintaining stem-cell
characteristics.
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