Tcf3: a transcriptional regulator of axis induction in the early embryo.
The roles of Lef/Tcf proteins in determining cell fate characteristics have been described in many contexts during vertebrate embryogenesis, organ and tissue homeostasis, and cancer formation. Although much of the accumulated work on these proteins involves their ability to transactivate target genes when stimulated by beta-catenin, Lef/Tcf proteins can repress target genes in the absence of stabilized beta-catenin. By ablating Tcf3 function, we have uncovered an important requirement for a repressor function of Lef/Tcf proteins during early mouse development. Tcf3-/- embryos proceed through gastrulation to form mesoderm, but they develop expanded and often duplicated axial mesoderm structures, including nodes and notochords. These duplications are preceded by ectopic expression of Foxa2, an axial mesoderm gene involved in node specification, with a concomitant reduction in Lefty2, a marker for lateral mesoderm. By contrast, expression of a beta-catenin-dependent, Lef/Tcf reporter (TOPGal), is not ectopically activated but is faithfully maintained in the primitive streak. Taken together, these data reveal a unique requirement for Tcf3 repressor function in restricting induction of the anterior-posterior axis.
Merrill
Bradley J
BJ
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021, USA.
Pasolli
H Amalia
HA
Polak
Lisa
L
Rendl
Michael
M
García-García
Maria J
MJ
Anderson
Kathryn V
KV
Fuchs
Elaine
E
D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D002490:Central Nervous System / Q000002:abnormalities; D003598:Cytoskeletal Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000502:physiology; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin