Complementary functions of Otx2 and Cripto in initial patterning of mouse epiblast
Complementary functions of Otx2 and Cripto in initial patterning of mouse epiblast
复制标题
DOI：
10.1006/dbio.2001.0289
复制
发表时间：
2001-07-01
影响因子：
2.7
通讯作者：
Matsuo, I
中科院分区：
文献类型：
--
作者：
Kimura, C;Shen, MM;Matsuo, I
哺乳动物前-后(A-P)轴的发育分别由不同的前、后信号中心、前内脏内胚层和原始条纹组成。对小鼠的基因敲除研究表明，OTX2和Cripto分别在这些前部和后部中枢的生成和/或功能中发挥关键作用。在OTX2和Cripto单突变体中，A-P轴的初始形成是在近端-远端(P-D)方向上发生的，但随后的轴旋转无法发生。为了研究这两个基因缺失的发育后果，我们分析了OTX2(-/-)；Cripto(-/-)双纯合子突变表型。在双突变体中，未诱导A-P轴标记Cer-1、Lim1和WNT3的表达，而Fgf8和T的表达扩大到整个上胚层，表明双突变体即使在其最初的P-D方向上也不能形成A-P轴。此外，这两个突变体在上胚层上的内脏内胚层的分化以及胚外外胚层的分化方面也存在缺陷。此外，双突变外胚层中Oct4的表达减少，Sox1和Gbx2的表达出现，表明神经外胚层的分化速度加快。由此产生的外胚层仅显示出前后脑的特征，这意味着它在哺乳动物的身体平面上是一种基本状态。我们的结果表明，OTX2和Cripto的互补功能对于小鼠胚胎A-P轴的初始模式是必不可少的。(C)2001年学术出版社。
The development of the mammalian antero-posterior (A-P) axis is proposed to be established by distinct anterior and posterior signaling centers, anterior visceral endoderm and primitive streak, respectively. Knock-out studies in mice have shown that Otx2 and Cripto have crucial roles in the generation and/or functions of these anterior and posterior centers, respectively. In both Otx2 and Cripto single mutants, the initial formation of the A-P axis takes place in a proximal-distal (P-D) orientation, but subsequent axis rotation fails to occur. To examine the developmental consequences of the lack of these two genes, we have analyzed the Otx2(-/-);Cripto(-/-) double homozygous mutant phenotype. In the double mutants, the expression of the A-P axis markers Cer-1, Lim1, and Wnt3 was not induced, while expression of Fgf8 and T was expanded throughout the epiblast, indicating that the double mutants could not form the A-P axis even in its initial P-D orientation. In addition, the double mutants displayed defects in differentiation of the visceral endoderm overlying the epiblast, as well as in the extraembryonic ectoderm. Furthermore, differentiation of neuroectoderm was accelerated as judged by the reduction of Oct4 expression and emergence of Sox1 and Gbx2 expression in the double mutant epiblast. The resulting ectoderm only displayed characteristics of anterior hindbrain, implicating it as a ground state in the mammalian body plan. Our results indicate that complementary functions of Otx2 and Cripto are essential for initial patterning of the A-P axis in the mouse embryo. (C) 2001 Academic Press.