Wnt/(beta)-catenin signaling regulates the expression of the homeobox gene Cdx1 in embryonic intestine.
During mammalian development, the Cdx1 homeobox gene exhibits an early period of expression when the embryonic body axis is established, and a later period where expression is restricted to the embryonic intestinal endoderm. Cdx1 expression is maintained throughout adulthood in the proliferative cell compartment of the continuously renewed intestinal epithelium, the crypts. In this study, we provide evidence in vitro and in vivo that Cdx1 is a direct transcriptional target of the Wnt/(beta)-catenin signaling pathway. Upon Wnt stimulation, expression of Cdx1 can be induced in mouse embryonic stem (ES) cells as well as in undifferentiated rat embryonic endoderm. Tcf4-deficient mouse embryos show abrogation of Cdx1 protein in the small intestinal epithelium, making Tcf4 the likely candidate to transduce Wnt signal in this part of gut. The promoter region of the Cdx1 gene contains several Tcf-binding motifs, and these bind Tcf/Lef1/(beta)-catenin complexes and mediate (beta)-catenin-dependent transactivation. The transcriptional regulation of the homeobox gene Cdx1 in the intestinal epithelium by Wnt/(beta)-catenin signaling underlines the importance of this signaling pathway in mammalian endoderm development.
Lickert
H
H
Department of Molecular Embryology, Max-Planck Institute of Immunobiology, Stübeweg 51, D-79108 Freiburg, Germany.
Domon
C
C
Huls
G
G
Wehrle
C
C
Duluc
I
I
Clevers
H
H
Meyer
B I
BI
Freund
J N
JN
Kemler
R
R
D016475:3T3 Cells; D000818:Animals; D030161:Avian Proteins; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004707:Endoderm; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000196:embryology; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D030161:Avian Proteins; C491273:CDX1 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C491272:Cdx1 protein, mouse; C491271:Cdx1 protein, rat; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; C497575:Lef1 protein, rat; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; C553059:Tcf7l2 protein, rat; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin