Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation
Copyright policy )Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation
Smad-interacting protein-1 (Sip1) [Zinc finger homeobox (Zfhx1b)] is a transcription factor implicated in the genesis of Mowat–Wilson syndrome in humans. Sip1 expression in the dorsal telencephalon of mouse embryos was documented from E12.5. We inactivated the gene specifically in cortical precursors. This resulted in the lack of the entire hippocampal formation. Sip1 mutant mice exhibited death of differentiating cells and decreased proliferation in the region of the prospective hippocampus and dentate gyrus. The expression of the Wnt antagonist Sfrp1 was ectopically activated, whereas the activity of the noncanonical Wnt effector, JNK, was down-regulated in the embryonic hippocampus of mutant mice. In cortical cells, Sip1 protein was detected on the promoter of Sfrp1 gene and both genes showed a mutually exclusive pattern of expression suggesting that Sfrp1 expression is negatively regulated by Sip1. Sip1 is therefore essential to the development of the hippocampus and dentate gyrus, and is able to modulate Wnt signaling in these regions.
- Osaka University Japan
- Max Planck Institute for Multidisciplinary Sciences Germany
- Ghent University Belgium
- KU Leuven Belgium
- Max Planck Society Germany
Telencephalon, knockout, hirschsprung-disease, Apoptosis, Hippocampus, Mice, BRAIN, Promoter Regions, Genetic, Stem Cells, sip1, MOWAT-WILSON-SYNDROME, Gene Expression Regulation, Developmental, Up-Regulation, Multidisciplinary Sciences, BINDING-PROTEIN, cortex, binding-protein, Science & Technology - Other Topics, SIP1, Intercellular Signaling Peptides and Proteins, MENTAL RETARDATION SYNDROME, Signal Transduction, EXPRESSION, brain, mowat-wilson-syndrome, mental retardation syndrome, expression, E-CADHERIN, Animals, gene, development, Zinc Finger E-box Binding Homeobox 2, Cell Proliferation, Homeodomain Proteins, Science & Technology, MUTATIONS, sfrp1, JNK Mitogen-Activated Protein Kinases, Membrane Proteins, HIRSCHSPRUNG-DISEASE, mutations, GENE, Repressor Proteins, Wnt Proteins, Gene Expression Regulation, Mutation, e-cadherin, Gene Deletion, telencephalon
Telencephalon, knockout, hirschsprung-disease, Apoptosis, Hippocampus, Mice, BRAIN, Promoter Regions, Genetic, Stem Cells, sip1, MOWAT-WILSON-SYNDROME, Gene Expression Regulation, Developmental, Up-Regulation, Multidisciplinary Sciences, BINDING-PROTEIN, cortex, binding-protein, Science & Technology - Other Topics, SIP1, Intercellular Signaling Peptides and Proteins, MENTAL RETARDATION SYNDROME, Signal Transduction, EXPRESSION, brain, mowat-wilson-syndrome, mental retardation syndrome, expression, E-CADHERIN, Animals, gene, development, Zinc Finger E-box Binding Homeobox 2, Cell Proliferation, Homeodomain Proteins, Science & Technology, MUTATIONS, sfrp1, JNK Mitogen-Activated Protein Kinases, Membrane Proteins, HIRSCHSPRUNG-DISEASE, mutations, GENE, Repressor Proteins, Wnt Proteins, Gene Expression Regulation, Mutation, e-cadherin, Gene Deletion, telencephalon
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