Nodal signaling is required for closure of the anterior neural tube in zebrafish.
Nodal signaling is required for closure of the anterior neural tube in zebrafish.
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DOI：
10.1186/1471-213x-7-126
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发表时间：
2007-11-08
影响因子：
--
通讯作者：
Liang JO
中科院分区：
文献类型：
--
作者：
Aquilina-Beck A;Ilagan K;Liu Q;Liang JO
结节是一种分泌型信号蛋白，在脊椎动物的发育过程中起着多种作用。在这里，我们确定了一个新的作用，Nodal信号调节关闭的嘴神经管的斑马鱼。我们发现，神经管在假定的前脑未能关闭在斑马鱼Nodal信号突变体。例如，将产生松果体的细胞不能从神经板的侧边缘移动到间脑的中线。Nodal信号突变体中的开放神经管可能部分是由于N-钙粘蛋白的功能降低，N-钙粘蛋白是一种在神经管中表达的细胞粘附分子，是神经管闭合所需的。在缺乏Nodal信号传导的鱼中，N-钙粘蛋白的表达和膜定位减少。此外，N-钙粘蛋白突变体和morphant具有与Nodal途径缺陷的突变体相似的松果体表型。TGFβ I型受体Taram-A（Taram-A*）细胞的活化形式的过表达自主地挽救了鱼类中的中内胚层形成，同时Nodal信号传导严重减少。我们发现Taram-A* 的过表达也纠正了他们的开放性神经管缺陷。这表明，在哺乳动物中，中胚层和内胚层有一个重要的作用，在调节关闭的前神经管的斑马鱼。这项工作有助于建立Nodal信号在神经形成中的作用，并表明Nodal信号的缺陷可能是人类神经管缺陷的基础，例如露脑畸形，这是一种致命的疾病，其特征是前脑中的神经管开放。
Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish. We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFβ Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish. This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain.