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Extracellular Matrix and Axonal Guidance in C. elegans

线虫的细胞外基质和轴突引导

基本信息

批准号：
7416580
负责人：
WILLIAM G WADSWORTH
金额：
$ 33.61万
依托单位：
UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-05-01 至 2009-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Nervous systems comprise a grid-like network of longitudinal and circumferential nerves. Several molecules have been found that guide circumferential migrations in C. elegans including UNC-6, the founding member of the netrin protein family. Little is known, however, about the molecular mechanisms that govern different responses individual migrating axons have to these guidance cues. These differences are important since they allow a variety of axon migration patterns to develop and a greater number of connections to form. Two approaches are proposed to study the molecular basis of the responses that axons have to guidance cues. First, genes are being identified and studied that affect the guidance of only subsets of circumferentially migrating axons. Specifically, these genes are required for migration patterns that are different from those of other circumferential axons. In one case, a gene has been found that is expressed in only a few neurons and which encodes a conserved cytoplasmic protein. This gene genetically interacts with genes encoding components of known axon guidance signaling pathways and is therefore a strong candidate for regulating neuron-specific axon guidance responses. Second, genetic screens are being used to isolate second site mutations that suppress the phenotypes of specific unc-6 mutations. These unc-6 mutations disrupt UNC-6 structural domains that are responsible for mediating distinct UNC-6 guidance activities. By isolating mutations that can suppress the phenotypes of these unc-6 mutations, proteins that interact with UNC-6 to help mediate the different UNC-6 activities might be identified. In a pilot screen, an extragenic mutation that reverts the uncoordinated movement and axon guidance defects caused by an unc-6 mutation has been recovered. Understanding the molecular mechanisms that control axon and cell guidance could prove critical for developing therapeutic agents that treat nerves damaged by injuries or disease.

描述（由申请人提供）：神经系统包括纵向和环向神经的网格状网络。已发现多种分子可引导线虫的圆周迁移，其中包括 UNC-6（netrin 蛋白家族的创始成员）。然而，人们对控制个体迁移轴突对这些引导信号的不同反应的分子机制知之甚少。这些差异很重要，因为它们允许形成多种轴突迁移模式并形成更多数量的连接。提出了两种方法来研究轴突对引导信号的反应的分子基础。首先，正在识别和研究仅影响圆周迁移轴突子集的引导的基因。具体来说，这些基因对于不同于其他圆周轴突的迁移模式是必需的。在一个案例中，人们发现一种基因仅在少数神经元中表达，并且编码一种保守的细胞质蛋白。该基因在遗传上与编码已知轴突引导信号通路成分的基因相互作用，因此是调节神经元特异性轴突引导反应的有力候选者。其次，遗传筛选用于分离抑制特定 unc-6 突变表型的第二位点突变。这些 unc-6 突变破坏了负责介导不同 UNC-6 指导活动的 UNC-6 结构域。通过分离可以抑制这些 unc-6 突变表型的突变，可以鉴定与 UNC-6 相互作用以帮助介导不同 UNC-6 活性的蛋白质。在试点筛选中，恢复了由 unc-6 突变引起的不协调运动和轴突引导缺陷的基因外突变已被恢复。了解控制轴突和细胞引导的分子机制对于开发治疗因损伤或疾病而受损的神经的治疗药物至关重要。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Axon response to guidance cues is stimulated by acetylcholine in Caenorhabditis elegans.

秀丽隐杆线虫中的乙酰胆碱会刺激轴突对引导信号的反应。

DOI：
10.1534/genetics.111.133546
发表时间：
2011
期刊：
Genetics
影响因子：
3.3
作者：
Xu,Yan;Ren,Xing-Cong;Quinn,ChristopherC;Wadsworth,WilliamG
通讯作者：
Wadsworth,WilliamG

A Statistically-Oriented Asymmetric Localization (SOAL) Model for Neuronal Outgrowth Patterning by Caenorhabditis elegans UNC-5 (UNC5) and UNC-40 (DCC) Netrin Receptors.

线虫 UNC-5 (UNC5) 和 UNC-40 (DCC) Netrin 受体神经元生长模式的统计导向不对称定位 (SOAL) 模型。

DOI：
10.1534/genetics.117.300460
发表时间：
2018
期刊：
Genetics
影响因子：
3.3
作者：
Limerick,Gerard;Tang,Xia;Lee,WonSuk;Mohamed,Ahmed;Al-Aamiri,Aseel;Wadsworth,WilliamG
通讯作者：
Wadsworth,WilliamG

Role of netrin UNC-6 in patterning the longitudinal nerves of Caenorhabditis elegans.

netrin UNC-6 在秀丽隐杆线虫纵向神经模式中的作用。