Complementary expression pattern of Zfhx1 genes Sip1 and deltaEF1 in the mouse embryo and their genetic interaction revealed by compound mutants.
In mouse embryos, the Zfhx1 transcription factor genes, Sip1 and deltaEF1, are expressed in complementary domains in many tissues. Their possible synergism in embryogenesis was investigated by comparing the phenotype of Sip1-/-;deltaEF1-/- double homozygotes with single homozygous embryos. Unexpectedly, in Sip1-/- embryos deltaEF1 was ectopically activated, suggesting a negative regulation of deltaEF1 expression by Sip1. Sip1-/-;deltaEF1-/- embryos were similar to Sip1-/- embryos in short somite production and developmental arrest around E8.5, but showed more severe defects in dorsal neural tube morphogenesis accompanied by a larger reduction of Sox2 expression, ascribable to the loss of the ectopic deltaEF1 expression. Sip1+/-;deltaEF1-/- embryos develop various morphological defects after E10 that were absent in deltaEF1-/- embryos even in tissues without significant overlap of Sip1 and deltaEF1 expression, and arrested during mid gestation earlier than deltaEF1-/- embryos. These findings indicate that complex synergistic interactions occur between Zfhx1 transcription factor genes during mouse embryogenesis.
Miyoshi
Tomoya
T
Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
Maruhashi
Mitsuji
M
Van De Putte
Tom
T
Kondoh
Hisato
H
Huylebroeck
Danny
D
Higashi
Yujiro
Y
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009436:Neural Tube Defects / Q000196:embryology / Q000378:metabolism; D009928:Organ Specificity; D010641:Phenotype; D055748:SOXB1 Transcription Factors; D019170:Somites / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; C491561:Sip1 protein, mouse; C527783:Sox2 protein, mouse; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1