title: Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation.
abstract: 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.
authors.affiliation: Max Planck Institute for Experimental Medicine, Hermann-Rein Strasse 3, 37075 Göttingen, Germany.
authors.forename: Amaya
authors.initials: A
authors.lastname: Miquelajauregui
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Putte
authors.forename: Alexander
authors.initials: A
authors.lastname: Polyakov
authors.forename: Anjana
authors.initials: A
authors.lastname: Nityanandam
authors.forename: Sridhar
authors.initials: S
authors.lastname: Boppana
authors.forename: Eve
authors.initials: E
authors.lastname: Seuntjens
authors.forename: Anton
authors.initials: A
authors.lastname: Karabinos
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Higashi
authors.forename: Danny
authors.initials: D
authors.lastname: Huylebroeck
authors.forename: Victor
authors.initials: V
authors.lastname: Tarabykin
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013687:Telencephalon / Q000378:metabolism; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D000074165:Zinc Finger E-box Binding Homeobox 2; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D008565:Membrane Proteins; D012097:Repressor Proteins; D051153:Wnt Proteins; D000074165:Zinc Finger E-box Binding Homeobox 2; C485539:Sfrp1 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C120602:ZEB2 protein, mouse