Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice.
Members of the LEF-1/TCF family of transcription factors have been implicated in the transduction of Wnt signals. However, targeted gene inactivations of Lef1, Tcf1, or Tcf4 in the mouse do not produce phenotypes that mimic any known Wnt mutation. Here we show that null mutations in both Lef1 and Tcf1, which are expressed in an overlapping pattern in the early mouse embryo, cause a severe defect in the differentiation of paraxial mesoderm and lead to the formation of additional neural tubes, phenotypes identical to those reported for Wnt3a-deficient mice. In addition, Lef1(-/-)Tcf1(-/-) embryos have defects in the formation of the placenta and in the development of limb buds, which fail both to express Fgf8 and to form an apical ectodermal ridge. Together, these data provide evidence for a redundant role of LEF-1 and TCF-1 in Wnt signaling during mouse development.
Galceran
J
J
Howard Hughes Medical Institute and Departments of Microbiology and Biochemistry, University of California, San Francisco, California 94143, USA.
Fariñas
I
I
Depew
M J
MJ
Clevers
H
H
Grosschedl
R
R
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D004622:Embryo, Mammalian / Q000648:ultrastructure; D051538:Hepatocyte Nuclear Factor 1-alpha; D017880:Limb Deformities, Congenital / Q000235:genetics*; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors / Q000235:genetics*; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011506:Proteins; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse