Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1

Lef1 and other genes of the LEF1/TCF family of transcription factors are nu clear mediators of Wnt signaling. Here we examine the expression pattern an d functional importance of Lef1 in the developing forebrain of the mouse. L ef1 is expressed in the developing hippocampus, and LEF1-deficient embryos lack dentate gyrus granule cells but contain glial cells and interneurons i n the region of the dentate gyrus. In mouse embryos homozygous for a Lef1-l acZ fusion gene, which encodes a protein that is not only deficient in DNA binding but also interferes with beta-catenin-mediated transcriptional acti vation by other LEF1/TCF proteins, the entire hippocampus including the CA fields is missing. Thus, LEF1 regulates the generation of dentate gyrus gra nule cells, and together with other LEF1/TCF proteins, the development of t he hippocampus.