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RESEARCH COMMUNICATION
1 Gene Center and Institute of Biochemistry, University of Munich, 81377 Munich, Germany; 2 Max-Planck-Institute of Immunobiology, 79108 Freiburg, Germany
Wnt signaling, which is mediated by LEF1/TCF transcription factors, has been placed upstream of the Notch pathway in vertebrate somitogenesis. Here, we examine the molecular basis for this presumed hierarchy and show that a targeted mutation of Lef1, which abrogates LEF1 function and impairs the activity of coexpressed TCF factors, affects the patterning of somites and the expression of components of the Notch pathway. LEF1 was found to bind multiple sites in the Dll1 promoter in vitro and in vivo. Moreover, mutations of LEF1-binding sites in the Dll1 promoter impair expression of a Dll1–LacZ transgene in the presomitic mesoderm. Finally, the induced expression of LEF1–
-catenin activates the expression of endogenous Dll1 in fibroblastic cells. Thus, Wnt signaling can affect the Notch pathway by a LEF1-mediated regulation of Dll1.
[Keywords: Somitogenesis; LEF1/TCF; Wnt; Notch; Dll1]
Received August 11, 2004; revised version accepted September 28, 2004.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1249504.
3 Present address: Instituto de Neurociencias, Campus San Juan, 03550 Sant Joan d'Alacant, Spain
4 Corresponding author. E-MAIL grosschedl{at}immunbio.mpg.de; FAX 49-761-5108-799.
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