Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain
Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain
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DOI：
10.1093/emboj/20.16.4454
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发表时间：
2001-08-15
期刊：
影响因子：
11.4
通讯作者：
Kageyama, R
中科院分区：
文献类型：
--
作者：
Hirata, H;Tomita, K;Kageyama, R
峡部组织者位于中脑-后脑交界处，在中脑和前后脑的发育中起着重要作用。研究表明，同源异型盒基因调控峡部组织者的形成，但维持组织者的机制尚不清楚。在这里，我们发现，在小鼠双突变的基本螺旋-环-螺旋基因Hes 1和Hes 3，中脑和前后脑结构丢失，没有任何显着的细胞死亡。在这些突变体中，峡部组织者细胞过早分化为神经元，并终止分泌分子如Fgf 8和Wnt 1以及配对盒基因Pax 2/5的表达，所有这些都是峡部组织者功能所必需的。这些结果表明，Hes 1和Hes 3防止过早分化和维持峡部细胞的组织者活性，从而调节中脑和前1-dndbrain的发育。
The isthmic organizer, which is located at the midbrain-hindbrain boundary, plays an essential role in development of the midbrain and anterior hindbrain. It has been shown that homeobox genes regulate establishment of the isthmic organizer, but the mechanism by which the organizer is maintained is not well understood. Here, we found that, in mice doubly mutant for the basic helix-loop-helix genes Hes1 and Hes3, the midbrain and anterior hindbrain structures are missing without any significant cell death. In these mutants, the isthmic organizer cells prematurely differentiate into neurons and terminate expression of secreting molecules such as Fgf8 and Wnt1 and the paired box genes Pax2/5, all of which are essential for the isthmic organizer function. These results indicate that Hes1 and Hes3 prevent premature differentiation and maintain the organizer activity of the isthmic cells, thereby regulating the development of the midbrain and anterior 1-dndbrain.