Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation

EXPRESSION Telencephalon brain knockout hirschsprung-disease Apoptosis Hippocampus mowat-wilson-syndrome Mice 03 medical and health sciences mental retardation syndrome E-CADHERIN expression Animals BRAIN gene Promoter Regions, Genetic development Cell Proliferation Homeodomain Proteins 0303 health sciences MUTATIONS sfrp1 Stem Cells MOWAT-WILSON-SYNDROME sip1 JNK Mitogen-Activated Protein Kinases Gene Expression Regulation, Developmental Membrane Proteins HIRSCHSPRUNG-DISEASE mutations GENE Up-Regulation Repressor Proteins Wnt Proteins BINDING-PROTEIN cortex Gene Expression Regulation binding-protein Mutation SIP1 Intercellular Signaling Peptides and Proteins MENTAL RETARDATION SYNDROME e-cadherin Gene Deletion telencephalon Signal Transduction
DOI: 10.1073/pnas.0609863104 Publication Date: 2007-07-21T00:48:49Z
ABSTRACT
Smad-interacting protein-1 (Sip1) [Zinc finger homeobox (Zfhx1b)] is a transcription factor implicated in the genesis of Mowat–Wilson syndrome humans. Sip1 expression dorsal telencephalon mouse embryos was documented from E12.5. We inactivated gene specifically cortical precursors. This resulted lack entire hippocampal formation. mutant mice exhibited death differentiating cells and decreased proliferation region prospective hippocampus dentate gyrus. The Wnt antagonist Sfrp1 ectopically activated, whereas activity noncanonical effector, JNK, down-regulated embryonic mice. In cells, protein detected on promoter both genes showed mutually exclusive pattern suggesting that negatively regulated by Sip1. therefore essential to development gyrus, able modulate signaling these regions.
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