Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion.
Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion.
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DOI：
10.1016/j.ydbio.2011.02.027
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发表时间：
2011-05-01
影响因子：
2.7
通讯作者：
Niswander L
中科院分区：
文献类型：
--
作者：
Pyrgaki C;Liu A;Niswander L
胚胎组织如神经管、体壁、面部和眼睛闭合缺陷会导致严重的出生缺陷。据推测，细胞黏附有助于神经管和体壁的闭合，然而这一过程潜在的分子调节因子尚未被确定。在此我们在小鼠中鉴定出一个ENU诱导的突变，它揭示了胚胎闭合的一个分子通路。Line2F纯合突变胚胎无法闭合神经管、体壁、面部和视裂，并且它们在肺和心脏发育方面也表现出缺陷。利用一种新的基因组序列捕获技术以及对小鼠基因组2.5 Mb区域的高通量测序，我们在类颗粒头蛋白2基因（Grhl2）中发现了一个突变。微阵列分析显示Grhl2影响一系列参与细胞黏附的基因的表达，并且在需要Grhl2功能的组织中E - 钙黏蛋白急剧减少。Grhl2突变体中的组织闭合缺陷与AP - 2α缺失突变体相似，并且已表明AP - 2α能与E - 钙黏蛋白的启动子结合。因此，我们测试了这些基因之间可能存在的相互作用。然而，我们发现Grhl2和AP - 2α并不调节彼此的表达，在神经管闭合期间AP - 2α突变体中E - 钙黏蛋白表达正常，并且Grhl2；AP - 2α反式杂合胚胎在形态上是正常的。综上所述，我们的研究指向神经管融合的复杂调控，并强调了对这两种模型进行比较以更全面地理解胚胎组织闭合的分子通路的重要性。
Defects in closure of embryonic tissues such as the neural tube, body wall, face and eye lead to severe birth defects. Cell adhesion is hypothesized to contribute to closure of the neural tube and body wall, however potential molecular regulators of this process have not been identified. Here we identify an ENU-induced mutation in mice that reveals a molecular pathway of embryonic closure. Line2F homozygous mutant embryos fail to close the neural tube, body wall, face, and optic fissure, and they also display defects in lung and heart development. Using a new technology of genomic sequence capture and high-throughput sequencing of a 2.5 Mb region of the mouse genome, we discovered a mutation in the grainyhead-like 2 gene (Grhl2). Microarray analysis revealed Grhl2 affects the expression of a battery of genes involved in cell adhesion and E-cadherin protein is drastically reduced in tissues that require Grhl2 function. The tissue closure defects in Grhl2 mutants are similar to that of AP-2α null mutants and AP-2α has been shown to bind to the promoter of E-cadherin. Therefore, we tested for a possible interaction between these genes. However, we find that Grhl2 and AP-2α do not regulate each other’s expression, E-cadherin expression is normal in AP-2α mutants during neural tube closure, and Grhl2;AP-2α trans-heterozygous embryos are morphologically normal. Taken together, our studies point to a complex regulation of neural tube fusion and highlight the importance of comparisons between these two models to understand more fully the molecular pathways of embryonic tissue closure.
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影响因子：
64.5
作者：
BIGGIN, MD;TJIAN, R
通讯作者：
TJIAN, R
DOI：
10.1073/pnas.0910267107
发表时间：
2010-02-02
影响因子：
11.1
作者：
An, Jee Young;Kim, Eun-A.;Kwon, Yong Tae
通讯作者：
Kwon, Yong Tae
影响因子：
10.5
作者：
Liaw, GJ;Rudolph, KM;Lengyel, JA
通讯作者：
Lengyel, JA
影响因子：
3.6
作者：
CHEN, BY;HALES, BF
通讯作者：
HALES, BF
影响因子：
2.6
作者：
Liu, AM;Joyner, AL;Turnbull, DH
通讯作者：
Turnbull, DH