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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A vital role for glycosphingolipid synthesis during development and differentiation
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A vital role for glycosphingolipid synthesis during development and differentiation

机译：在发育和分化过程中糖鞘脂合成的至关重要的作用

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Glycosphingolipids (GSLs) are believed to be integral for the dynamics of many cell membrane events, including cellular interactions, signaling, and trafficking. We have investigated their roles in development and differentiation by eliminating the major synthesis pathway of GSLs through targeted disruption of the Ugeg gene encoding glucosylceramide synthase. In the absence of GSL synthesis, embryogenesis proceeded well into gastrulation with differentiation into primitive germ layers and patterning of the embryo but was abruptly halted by a major apoptotic process. In vivo, embryonic stem cells defficient in GSL synthesis were again able to differentiate iuto endodermal, mesodermal, and ectodermal derivatives but were strikingly deficient in their ability to form well differentiated tissues. In vitro, however, hematopoietic and neuronal differentiation could be induced. The results demonstrate that the synthesis of GSL structures is essential for embryonic development and for the differentiation of some tissues and support the concept that GSLs are involved in crucial cell interactions mediating these processes.
机译：人们认为糖鞘脂（GSL）是许多细胞膜事件（包括细胞相互作用，信号传导和运输）的动力学必不可少的。我们已经通过靶向性破坏编码葡萄糖基神经酰胺合酶的Ugeg基因消除了GSL的主要合成途径，从而研究了它们在发育和分化中的作用。在没有GSL合成的情况下，胚发生进展到胃形成，分化为原始胚层和胚胎模式，但由于主要的凋亡过程而突然停止。在体内，GSL合成效率低下的胚胎干细胞再次能够区分内胚层，中胚层和外胚层衍生物，但是它们形成良好分化组织的能力却明显不足。然而，在体外，可以诱导造血和神经元分化。结果表明，GSL结构的合成对于胚胎发育和某些组织的分化是必不可少的，并支持GSL参与介导这些过程的关键细胞相互作用的概念。

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