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.
Miquelajauregui
Amaya
A
Max Planck Institute for Experimental Medicine, Hermann-Rein Strasse 3, 37075 Göttingen, Germany.
Van de Putte
Tom
T
Polyakov
Alexander
A
Nityanandam
Anjana
A
Boppana
Sridhar
S
Seuntjens
Eve
E
Karabinos
Anton
A
Higashi
Yujiro
Y
Huylebroeck
Danny
D
Tarabykin
Victor
V
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
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