Braun Michelle M, Etheridge Alton, Bernard Amy, Robertson Christie P, Roelink Henk
Program in Neurobiology and Behavior, Department of Biological Structure, Box 357420, University of Washington, Seattle, WA 98195, USA.
Development. 2003 Dec;130(23):5579-87. doi: 10.1242/dev.00685. Epub 2003 Oct 1.
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.
发育中的大脑前后模式形成的最早表现之一，是Six3和Irx3分别在前脑前部和后部的限制性表达。与Wnt作为神经组织中使后部化因子的作用一致，我们发现Wnt信号足以在前脑外植体中诱导Irx3表达并抑制Six3表达。丘脑间限制带（zli）是在腹侧丘脑（vT）和背侧丘脑（dT）之间发育的边界细胞群，其位置由Six3和Irx3表达域的并置所预测。几种诱导分子的表达模式受zli限制，包括Wnt3，它在dT中zli的后方表达。Wnt3和Wnt3a足以仅在假定zli后方分离的外植体中诱导dT标记物Gbx2。阻断Wnt反应可在前体dT组织中诱导vT特异性标记物Dlx2的表达。在dT中Six3的错误表达诱导了Dlx2的表达，并抑制了Gbx2和Wnt3的表达。这些结果证明了Wnt信号在前脑发育中的双重作用。首先，Wnt在前脑中指导Irx3的初始表达和Six3的抑制，划分了前脑后部和前部区域。后来，持续的Wnt信号导致dT特异性标记物的诱导，但仅在表达Irx3的组织中。
