Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation
Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation
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DOI：
10.1242/dev.137315
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发表时间：
2017-04-15
期刊：
影响因子：
4.6
通讯作者：
Borodinsky, Laura N.
中科院分区：
文献类型：
--
作者：
Balashova, Olga A.;Visina, Olesya;Borodinsky, Laura N.
补充叶酸可以预防高达70%的神经管缺陷（NTD），神经管缺陷是由于胚胎发生期间神经管闭合失败而导致的。阐明叶酸作用的机制一直是一个挑战。本研究介绍非洲爪蟾作为一个模型，以确定参与叶酸作用在神经管形成的细胞和分子机制。我们发现，叶酸受体1（Folr 1;也称为FRa）的敲低损害神经管的形成，并导致NTDs。仅在神经板细胞中敲低Folr 1是诱导NTDs所必需的且足够的。Foll 1缺陷的神经板细胞不能收缩，导致神经板中线加宽和神经管闭合缺陷。在神经胚形成期间，甲氨蝶呤对叶酸作用的药理学抑制通过抑制叶酸与其摄取系统的相互作用诱导NTDs。我们的研究结果支持一种模型，其中叶酸受体与细胞粘附分子相互作用，从而调节神经板折叠所需的顶端细胞膜重塑和细胞骨架动力学。对这种生物体的进一步研究可以揭示叶酸介导的新的细胞和分子事件，并导致预防NTD的新方法。
Folate supplementation prevents up to 70% of neural tube defects (NTDs), which result from a failure of neural tube closure during embryogenesis. The elucidation of the mechanisms underlying folate action has been challenging. This study introduces Xenopus laevis as a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor 1 (Folr1; also known as FRa) impairs neural tube formation and leads to NTDs. Folr1 knockdown in neural plate cells only is necessary and sufficient to induce NTDs. Folr1-deficient neural plate cells fail to constrict, resulting in widening of the neural plate midline and defective neural tube closure. Pharmacological inhibition of folate action by methotrexate during neurulation induces NTDs by inhibiting folate interaction with its uptake systems. Our findings support a model in which the folate receptor interacts with cell adhesion molecules, thus regulating the apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism could unveil novel cellular and molecular events mediated by folate and lead to new ways of preventing NTDs.