Wnt signaling is required at distinct stages of development for the induction of the posterior forebrain
Wnt signaling is required at distinct stages of development for the induction of the posterior forebrain
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DOI：
10.1242/dev.00685
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发表时间：
2003-12-01
期刊：
影响因子：
4.6
通讯作者：
Roelink, H
中科院分区：
文献类型：
--
作者：
Braun, MM;Etheridge, A;Roelink, H
在发育中的大脑中，最早期的表现之一是Six3和Irx3分别在前脑和后前脑的限制性表达。与Wnt在神经组织中作为后植剂的作用一致，我们发现Wnt信号足以诱导Irx3并抑制前脑外植体中Six3的表达。分区的位置受到限制；丘脑内（zli）是在腹侧丘脑（vT）和背侧丘脑（dT）之间发育的一种边界细胞群，可以通过Six3和Irx3表达域的相对性来预测。一些诱导分子的表达模式受到zli的限制，包括Wnt3，它在dT中表达在zli后。Wnt3和Wnt3a足以在推定zli后分离的外植体中诱导dT标记Gbx2。阻断Wnt反应可以在预期的dT组织中诱导vt特异性标记物Dlx2。在dT中错表达Six3诱导Dlx2表达，抑制Gbx2和Wnt3的表达。这些结果表明Wnt信号在前脑发育中具有双重作用。首先，wnt在前脑中指导Irx3的初始表达和Six3的抑制，描绘前脑后区和前脑区。随后，持续的Wnt信号传导导致dT特异性标记物的诱导，但仅在表达Irx3的组织中。
One of the earliest manifestations of anteroposterior pattering in the developing brain is the restricted expression of Six3 and Irx3 in the anterior and posterior forebrain, respectively. Consistent with the role of Wnts as posteriorizing agents in neural tissue, we found that Wnt signaling was sufficient to induce Irx3 and repress Six3 expression in forebrain explants. The position of the zona limitans; intrathalamica (zli), a boundary-cell population that develops between the ventral (vT) and dorsal thalamus (dT), is predicted by the apposition of Six3 and Irx3 expression domains. The expression patterns of several inductive molecules are limited by the zli, including Wnt3, which is expressed posterior to the zli in the dT. Wnt3 and Wnt3a were sufficient to induce the dT marker Gbx2 exclusively in explants isolated posterior to the presumptive zli. Blocking the Wnt response allowed the induction of the vT-specific marker Dlx2 in prospective dT tissue. Misexpression of Six3 in the dT induced Dlx2 expression and inhibited the expression of both Gbx2 and Wnt3. These results demonstrate a dual role for Wnt signaling in forebrain development. First, Wnts directed the initial expression of Irx3 and repression of Six3 in the forebrain, delineating posterior and anterior forebrain domains. Later, continued Wnt signaling resulted in the induction of dT specific markers, but only in tissues that expressed Irx3.