Evolution of the Developing Myelin Sheath

9986132Gould本研究项目的长期目标是了解少突胶质细胞（和许旺细胞）如何髓鞘化轴突。 意识到参与髓鞘形成的早期识别和组装阶段的蛋白质都是未知的，开发了一种策略，通过分离代表位于髓鞘组装位点的信使RNA的互补DNA分子来鉴定这些蛋白质。 对其中一些mRNA的发育表达模式的研究（鉴定了80多种）表明，它们分为两个发育组。 一组直到髓鞘形成进行良好时（大鼠出生后第10天）才强烈表达。 第二组在数量上几乎与第一组相同，表达较早，并且在具有较小有髓纤维的组织中具有较高的表达。 利用用于鉴定这些mRNA的技术，将进行研究以鉴定第三组mRNA，这些mRNA在少突胶质细胞过程首次接触它们将形成髓鞘的轴突时优先表达。 一旦这些mRNA被鉴定，将进行研究以定位mRNA和蛋白质在发育中的神经系统中表达的位点，以确保这些蛋白质确实对髓鞘形成的早期阶段很重要。 有髓神经系统是所有有颌脊椎动物的共同祖先，包括软骨鱼类和硬骨鱼、两栖动物、爬行动物、鸟类和哺乳动物。 这种发展需要招募蛋白质，使髓鞘形成在共同的祖先中发生。 老鼠和鲨鱼之间的比较研究正在计划中，并将用于帮助我们了解有髓鞘神经系统是如何起源的。

9986132Gould The long-term goal of this research project is to gain understanding of how oligodendrocytes (and Schwann cells) myelinate axons. Realizing that none of the proteins involved in the early recognition and assembly stages of myelination were unknown, a strategy was developed to identify such proteins through isolation of complementary DNA molecules that represent messenger RNAs located at sites where myelin sheaths assemble. Studies of the developmental expression patterns of some of these mRNAs (over 80 were identified) showed that they fell into two developmental groups. One group was not strongly expressed until myelination was well under way (postnatal day 10 in rat). A second group, nearly equal in number to the first group, was expressed earlier and had higher expression in tissues with smaller myelinated fibers. With techniques used to identify these mRNAs, studies will be conducted to identify a third group of mRNAs, those expressed preferentially at times that oligodendrocyte processes first contact the axons they will myelinate. Once these mRNAs are identified, studies will be conducted to locate the sites where mRNAs and proteins are expressed in the developing nervous system to insure that the proteins are indeed important for early stages of myelination. The myelinated nervous system evolved in a common ancestor of all jawed vertebrates, including cartilaginous and teleost fishes, amphibians, reptiles, birds and mammals. This development required recruitment of proteins that allowed myelination to take place in the common ancestor. Comparative studies between rats and sharks are planned and will be used to help us understand how the myelinated nervous system originated.