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（和雪旺细胞）是如何形成轴突的。意识到参与髓鞘形成早期识别和组装阶段的蛋白质都是未知的，研究人员开发了一种策略，通过分离髓鞘组装位点上代表信使rna的互补DNA分子来识别这些蛋白质。对其中一些mrna的发育表达模式的研究（鉴定了80多种）表明，它们可分为两个发育组。一组直到髓鞘形成良好（大鼠出生后第10天）才强烈表达。第二组在数量上与第一组几乎相等，在有髓纤维较小的组织中表达得更早，表达量更高。利用鉴定这些mrna的技术，研究将进行鉴定第三组mrna的研究，这些mrna在少突胶质细胞过程第一次接触轴突时优先表达，它们将形成髓鞘。一旦这些mrna被识别出来，研究将进行定位mrna和蛋白质在发育中的神经系统中表达的位置，以确保这些蛋白质确实对髓鞘形成的早期阶段很重要。髓鞘神经系统在所有有颌脊椎动物的共同祖先中进化而来，包括软骨鱼和硬骨鱼、两栖动物、爬行动物、鸟类和哺乳动物。这种发展需要蛋白质的补充，使髓鞘形成发生在共同的祖先身上。计划对老鼠和鲨鱼进行比较研究，并将用于帮助我们了解髓鞘神经系统的起源。

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.