RESUMO
Lef1 and other genes of the LEF1/TCF family of transcription factors are nuclear mediators of Wnt signaling. Here we examine the expression pattern and functional importance of Lef1 in the developing forebrain of the mouse. Lef1 is expressed in the developing hippocampus, and LEF1-deficient embryos lack dentate gyrus granule cells but contain glial cells and interneurons in the region of the dentate gyrus. In mouse embryos homozygous for a Lef1-lacZ fusion gene, which encodes a protein that is not only deficient in DNA binding but also interferes with (beta)-catenin-mediated transcriptional activation by other LEF1/TCF proteins, the entire hippocampus including the CA fields is missing. Thus, LEF1 regulates the generation of dentate gyrus granule cells, and together with other LEF1/TCF proteins, the development of the hippocampus.
Assuntos
Proteínas de Ligação a DNA/genética , Giro Denteado/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Hipocampo/embriologia , Prosencéfalo/embriologia , Fatores de Transcrição/genética , Animais , Apoptose , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/fisiologia , Giro Denteado/citologia , Desenvolvimento Embrionário e Fetal , Hipocampo/citologia , Homozigoto , Interneurônios/citologia , Interneurônios/fisiologia , Fator 1 de Ligação ao Facilitador Linfoide , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Neuroglia/citologia , Neuroglia/fisiologia , Prosencéfalo/citologia , Proteínas Recombinantes/biossíntese , Fatores de Transcrição/deficiência , Fatores de Transcrição/fisiologia , Ativação Transcricional , Transfecção , Células Tumorais Cultivadas , beta-Galactosidase/genéticaRESUMO
There is a long-standing controversy regarding the mechanisms that generate the functional subdivisions of the cerebral neocortex. One model proposes that thalamic axonal input specifies these subdivisions; the competing model postulates that patterning mechanisms intrinsic to the dorsal telencephalon generate neocortical regions. Gbx-2 mutant mice, whose thalamic differentiation is disrupted, were investigated. Despite the lack of cortical innervation by thalamic axons, neocortical region-specific gene expression (Cadherin-6, EphA-7, Id-2, and RZR-beta) developed normally. This provides evidence that patterning mechanisms intrinsic to the neocortex specify the basic organization of its functional subdivisions.