Transcription factor TEAD2 is involved in neural tube closure.
TEAD2, one of the first transcription factors expressed at the beginning of mammalian development, appears to be required during neural development. For example, Tead2 expression is greatest in the dorsal neural crest where it appears to regulate expression of Pax3, a gene essential for brain development. Consistent with this hypothesis, we found that inactivation of the Tead2 gene in mice significantly increased the risk of exencephaly (a defect in neural tube closure). However, none of the embryos exhibited spina bifida, the major phenotype of Pax3 nullizygous embryos, and expression of Pax3 in E11.5 Tead2 nullizygous embryos was normal. Thus, Tead2 plays a role in neural tube closure that is independent of its putative role in Pax3 regulation. In addition, the risk of exencephaly was greatest with Tead2 nullizygous females, and could be suppressed either by folic acid or pifithrin-alpha. These results reveal a maternal genetic contribution to neural tube closure, and suggest that Tead2-deficient mice provide a model for anencephaly, a common human birth defect that can be prevented by folic acid.
Kaneko
Kotaro J
KJ
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Kohn
Matthew J
MJ
Liu
Chengyu
C
DePamphilis
Melvin L
ML
D000483:Alleles; D000757:Anencephaly / Q000235:genetics; D000818:Animals; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics; D054259:Neural Tube / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D011247:Pregnancy; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D000091262:TEA Domain Transcription Factors; C486310:Tead2 protein, mouse; C101204:Tead4 protein, mouse; D014157:Transcription Factors; C068686:Pax3 protein, mouse; C496372:Fgfr4 protein, mouse; D051499:Receptor, Fibroblast Growth Factor, Type 4