Netrins Creating Divergent Axon Morphologies

描述（由申请人提供）：在神经系统发育过程中，轴突必须生长并与体内的目标建立适当的连接。近年来，许多调节这一过程的分子的发现使我们在理解轴突如何找到它们的目标方面取得了很大的进展。令人惊讶的是，许多引导轴突生长锥的分子在极端不同的生物体中是保守的。例如，Netrin蛋白在从果蝇到老鼠的各种生物中调节轴突向中线的生长。迄今为止，研究主要集中在生物间轴突引导的相似性上。这些发现虽然令人着迷，但却未能解释不同生物体中不同的神经网络模式是如何产生的。本研究旨在研究新的轴突形态产生的分子机制。本研究的具体目的是：(1)克隆两种轴突形态截然不同的甲壳类动物（Artemia franciscana和Parhyale hawaiensis）的netrin基因，(2)分析这些基因在Artemia和Parhyale发育过程中与轴突生长相关的表达模式，(3)将这些基因的表达模式与果蝇（Drosophila melanogaster）的表达模式进行比较，后者是一种已证实netrin基因功能的模式生物。这项工作，特别是对Artemia的分析，其轴突不能向中线生长，可能会提高对轴突引导分子如何被用来创造新的神经回路模式的基本理解。这可能有助于更好地理解人类复杂的神经回路模式是如何产生的。了解用于创建复杂神经网络的基本机制，也许有一天能让我们在遭受神经创伤的病人身上重建这种复杂的网络。

DESCRIPTION (provided by applicant): During nervous system development, axons must grow and make proper connections with their targets within the body. In recent years, the discovery of numerous molecules that regulate this process has allowed us to make great strides in understanding how axons find their targets. Surprisingly, many of the molecules that guide axonal growth cones are conserved amongst extremely divergent organisms. For example, Netrin proteins regulate growth of axons toward the midline in a wide variety of organisms, from fruit flies to mice. To date, research has mainly concentrated on the similarities in axon guidance amongst organisms. Such discoveries, while fascinating, have failed to explain how different neural network patterns have arisen in divergent organisms. This investigation aims to examine the molecular mechanisms underlying the creation of novel axonal morphologies. The specific aims of this investigation are: (1) to clone the netrin genes from Artemia franciscana and Parhyale hawaiensis, two crustaceans with extremely different axonal morphologies, (2) to analyze the expression patterns of these genes in relation to growing axons during Artemia and Parhyale development, and (3) to compare these expression patterns to those found in Drosophila melanogaster, a model organism in which the function of netrin genes is well documented. This work, particularly the analysis of Artemia, whose axons fail to grow toward the midline, will likely improve the basic understanding of how axonal guidance molecules can be used to create novel neural circuitry patterns. This could lead to a better understanding of how the complex neural circuitry patterns found in humans have arisen. Understanding the basic mechanisms that are used to create complex neural networks may someday enable us to recreate such complex networks in patients suffering from neural traumas.