title: Hindgut defects and transformation of the gastro-intestinal tract in Tcf4(-/-)/Tcf1(-/-) embryos.
abstract: Wnt signalling plays a critical role in both initiating and patterning of the anterior-posterior axis during development. Wnts exert their biological effects, in part, by activating specific target genes through members of the TCF/LEF family of transcription factors. To gain new insight into the role of T-cell factors (or Tcf's) during development, we analysed Tcf4 and Tcf1 compound null embryos. These mutants showed severe caudal truncations, as well as duplications of the neural tube. Unlike other mutations affecting Wnt signalling, paraxial mesoderm formation was not impaired and early caudal markers, such as T, were unaffected. Analysis of endodermal markers uncovered early and specific defects in hindgut expansion, and later an anterior transformation of the gastro-intestinal tract. Our results reveal a novel role for Wnt signalling in early gut morphogenesis and suggest that specific Wnt-driven patterning events are determined by the unique tissue distribution of Tcf/Lef family members.
authors.affiliation: Netherlands Institute for Developmental Biology and Center for Biomedical Genetics, Hubrecht Laboratory, Uppsalalaan, CT Utrecht, The Netherlands.
authors.forename: Alex
authors.initials: A
authors.lastname: Gregorieff
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grosschedl
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*; D004707:Endoderm / Q000378:metabolism / Q000473:pathology; D041981:Gastrointestinal Tract / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009436:Neural Tube Defects / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051820:TCF Transcription Factors; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C496496:Hnf1b protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051820:TCF Transcription Factors; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051153:Wnt Proteins; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta