Neural induction in Xenopus: requirement for ectodermal and endomesodermal signals via Chordin, Noggin, beta-Catenin, and Cerberus.
Neural induction in Xenopus: requirement for ectodermal and endomesodermal signals via Chordin, Noggin, beta-Catenin, and Cerberus.
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DOI：
10.1371/journal.pbio.0020092
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发表时间：
2004-05
期刊：
影响因子：
9.8
通讯作者：
De Robertis EM
中科院分区：
文献类型：
--
作者：
Kuroda H;Wessely O;De Robertis EM
诱导中枢神经系统（CNS）分化的信号起源是脊椎动物胚胎学中长期存在的问题。在这里，我们表明非洲爪蟾的神经诱导比之前想象的更早开始，即在囊胚阶段，并且需要两个不同信号中心的联合活动。其中之一是著名的 Nieuwkoop 中心，位于背侧植物细胞中，表达 Nodal 相关的内中胚层诱导物。另一个是位于背侧动物细胞中的囊胚脊索蛋白和头蛋白表达（BCNE）中心，其中包含未来神经外胚层和斯佩曼组织者前体细胞。两个中心都位于早期 β-连环蛋白信号的下游。分子分析表明BCNE中心与Nieuwkoop中心不同，并且Nieuwkoop中心表达分泌蛋白Cerberus (Cer)。我们发现，尚未接触中胚层基质的外植囊胚背侧动物帽细胞在盐水溶液中培养时可以表达明确的神经标记物并在组织学上分化为中枢神经系统组织。移植实验表明，BCNE 区域是大脑形成所必需的，尽管它在腹侧移植时缺乏 CNS 诱导活性。细胞谱系研究表明，BCNE 细胞形成大脑和视网膜的大部分，并在胚胎的后部区域形成底板和脊索。反义吗啉寡核苷酸 (MO) 的功能丧失实验表明，在无中胚层的非洲爪蟾胚胎（通过注射 Cerberus-Short [CerS] mRNA 产生）中形成的 CNS 需要 Chordin (Chd)、Noggin (Nog) 及其上游调节因子 β-Catenin。当背侧边缘区外植体中中胚层复旧被阻止时，外胚层中形成的前神经组织源自BCNE细胞，并且对Chd有完整的需求。通过将 Chd 吗啉寡核苷酸 (Chd-MO) 注射到 8 细胞阶段的未来神经外胚层中，将 Cerberus 吗啉寡核苷酸 (Cer-MO) 注入到未来的内中胚层中，我们发现这两层在 CNS 形成中相互配合。结果提出了非洲爪蟾的神经诱导模型，其中早期囊胚β-连环蛋白信号使未来的神经外胚层易于通过斯佩曼组织器发出的内中胚层信号进行神经诱导。对神经诱导早期事件的新见解，使某些细胞能够对斯佩曼组织者发出的信号做出反应
The origin of the signals that induce the differentiation of the central nervous system (CNS) is a long-standing question in vertebrate embryology. Here we show that Xenopus neural induction starts earlier than previously thought, at the blastula stage, and requires the combined activity of two distinct signaling centers. One is the well-known Nieuwkoop center, located in dorsal-vegetal cells, which expresses Nodal-related endomesodermal inducers. The other is a blastula Chordin- and Noggin-expressing (BCNE) center located in dorsal animal cells that contains both prospective neuroectoderm and Spemann organizer precursor cells. Both centers are downstream of the early β-Catenin signal. Molecular analyses demonstrated that the BCNE center was distinct from the Nieuwkoop center, and that the Nieuwkoop center expressed the secreted protein Cerberus (Cer). We found that explanted blastula dorsal animal cap cells that have not yet contacted a mesodermal substratum can, when cultured in saline solution, express definitive neural markers and differentiate histologically into CNS tissue. Transplantation experiments showed that the BCNE region was required for brain formation, even though it lacked CNS-inducing activity when transplanted ventrally. Cell-lineage studies demonstrated that BCNE cells give rise to a large part of the brain and retina and, in more posterior regions of the embryo, to floor plate and notochord. Loss-of-function experiments with antisense morpholino oligos (MO) showed that the CNS that forms in mesoderm-less Xenopus embryos (generated by injection with Cerberus-Short [CerS] mRNA) required Chordin (Chd), Noggin (Nog), and their upstream regulator β-Catenin. When mesoderm involution was prevented in dorsal marginal-zone explants, the anterior neural tissue formed in ectoderm was derived from BCNE cells and had a complete requirement for Chd. By injecting Chd morpholino oligos (Chd-MO) into prospective neuroectoderm and Cerberus morpholino oligos (Cer-MO) into prospective endomesoderm at the 8-cell stage, we showed that both layers cooperate in CNS formation. The results suggest a model for neural induction in Xenopus in which an early blastula β-Catenin signal predisposes the prospective neuroectoderm to neural induction by endomesodermal signals emanating from Spemann's organizer. New insights into the early events of neural induction which render certain cells competent to respond to signals emanating from Spemann's organizer