Kaneko Kotaro J, Kohn Matthew J, Liu Chengyu, DePamphilis Melvin L
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Genesis. 2007 Sep;45(9):577-87. doi: 10.1002/dvg.20330.
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.
TEAD2是哺乳动物发育开始时最早表达的转录因子之一，在神经发育过程中似乎是必需的。例如，Tead2在背侧神经嵴中表达最高，在那里它似乎调节Pax3的表达，Pax3是大脑发育所必需的基因。与这一假设一致，我们发现小鼠中Tead2基因的失活显著增加了无脑畸形（神经管闭合缺陷）的风险。然而，没有一个胚胎表现出脊柱裂，Pax3纯合缺失胚胎的主要表型，并且E11.5期Tead2纯合缺失胚胎中Pax3的表达是正常的。因此，Tead2在神经管闭合中发挥作用，这与其在Pax3调节中的假定作用无关。此外，Tead2纯合缺失雌性小鼠无脑畸形的风险最大，并且可以被叶酸或pifithrin-α抑制。这些结果揭示了母体基因对神经管闭合的贡献，并表明Tead2缺陷小鼠为无脑畸形提供了一个模型，无脑畸形是一种常见的人类出生缺陷，可以通过叶酸预防。
