Developmental expression of Wnt signaling factors in mouse brain.
The Wnt signaling pathway has been implicated in a variety of biological events inducing neurogenesis. In this study, we aim to investigate the expression pattern of various components of the Wnt pathway including b-catenin and its partners LEF-1/TCF-4, GSK-3beta and their nuclear target genes such as c-myc and cyclin D1 during mouse brain development. We performed a series of Western blot and immunohistochemistry of brain cortex, brainstem, and cerebellum which revealed differential accumulation of these proteins in different types of brain cells including neurons, astrocytes, and oligodendrocytes at different developmental stages. Intense cytoplasmic immunolabeling of beta-catenin in 5 day old neurons throughout the cortex and brainstem significantly decreased as the brain developed, whereas the level of GSK-3beta, the protein that phosphorylates beta-catenin and causes its destabilization, increased during brain maturation. On the other hand, high level accumulation of LEF-1 and TCF-4 in neurons and astrocytes at the early stage of brain development diminished at the later stages. Interestingly, while the majority of LEF-1 and TCF-4 immunoreactivity was detected in the cytoplasm of neurons, it was evident that both proteins accumulated in the nuclei of astrocytes. Examination of cyclin D1, a protein that controls the cell cycle and proliferation, exhibited an intense staining in the nuclei of astrocytes throughout brain parenchyma during development. Interestingly, cyclin D was found in the cytoplasm of neurons from cortex, brainstem, and cerebellum during brain development. These data provide compelling evidence for the differential expression of the Wnt signaling pathway during brain development, and suggest that these signaling pathways may function differently in various brain regions and cell types.
Coyle-Rink
Jacquelyn
J
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
Del Valle
Luis
L
Sweet
Thersa
T
Khalili
Kamel
K
Amini
Shohreh
S
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002467:Cell Nucleus; D019938:Cyclin D1 / Q000378:metabolism*; D003593:Cytoplasm; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D004676:Myelin Basic Protein; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D051820:TCF Transcription Factors; C544895:Tcf7l2 protein, mouse; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D019938:Cyclin D1; D011505:Protein-Tyrosine Kinases; D038362:Glycogen Synthase Kinase 3