Miz1 is required for early embryonic development during gastrulation.
Miz1 is a member of the POZ domain/zinc finger transcription factor family. In vivo, Miz1 forms a complex with the Myc oncoprotein and recruits Myc to core promoter elements. Myc represses transcription through Miz1 binding sites. We now show that the Miz1 gene is ubiquitously expressed during mouse embryogenesis. In order to elucidate the physiological function of Miz1, we have deleted the mouse Miz1 gene by homologous recombination. Miz1(+/-) mice are indistinguishable from wild-type animals; in contrast, Miz1(-/-) embryos are not viable. They are severely retarded in early embryonic development and do not undergo normal gastrulation. Expression of Goosecoid and Brachyury is detectable in Miz1(-/-) embryos, suggesting that Miz1 is not required for signal transduction by Nodal. Expression of p21Cip1, a target gene of Miz1 is unaltered; in contrast, expression of p57Kip2, another target gene of Miz1 is absent in Miz1(-/-) embryos. Miz1(-/-) embryos succumb to massive apoptosis of ectodermal cells around day 7.5 of embryonic development. Our results show that Miz1 is required for early embryonic development during gastrulation.
Adhikary
Sovana
S
Institute for Molecular Biology and Tumor Research. Institute for Cytobiology and Cytopathology, University of Marburg, 35033 Marburg, Germany.
Peukert
Karen
K
Karsunky
Holger
H
Beuger
Vincent
V
Lutz
Werner
W
Elsässer
Hans-Peter
HP
Möröy
Tarik
T
Eilers
Martin
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D005326:Fetal Proteins; D005775:Gastrula / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D020825:T-Box Domain Proteins / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins; D000098908:Brachyury Protein
D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005326:Fetal Proteins; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000098908:Brachyury Protein; C493956:CDKN1A protein, human; C493964:CDKN1C protein, human; C493966:CDKN2B protein, human; C493957:Cdkn1a protein, mouse; C493965:Cdkn1c protein, mouse; C493968:Cdkn2b protein, mouse; C497993:Gsc protein, mouse; C107961:ZBTB17 protein, human