NETRINS AND SEMAPHORINS AND AXONAL GUIDANCE
Netrins 和 Semaphorins 以及轴突引导
基本信息
- 批准号:2637767
- 负责人:
- 金额:$ 25.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-04-01 至 2002-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
This proposal will examine the role of netrins and semaphorins for axon
guidance in the zebrafish. The discovery of semaphorins and netrins has
lead to an appreciation of chemoattractive and repulsive mechanisms for
axon guidance. However, our understanding of the in vivo action of
these molecules is still incomplete. 1. The semaphorins are a large
family of molecules, but aspects of their function is only known for 3
semaphorins. This proposal will examine the in vivo action of 2 more
semaphorins. 2. It is clear that several mechanisms work coordinately
to guide axons. We now have some understanding of how individual
netrins and semaphorins work, but do not yet know how these molecules
work together to guide specific growth cones. This proposal will see how
these molecules work in concert to guide spinal commissural axons. 3.
Commissural growth cones first extend toward the midline and then away
from the midline in the CNS. How they do this despite the presence of
bilaterally symmetric guidance cues, such as chemoattractive netrins
expressed at the ventral midline of the CNS, is not well understood.
This proposal tests a mechanism that accounts for this behavior.
Based upon our analysis of netrins and semaphorins in zebrafish and the
actions of these molecules in other organisms, a model that incorporates
2 netrins and 2 semaphorins was generated to account for pathfinding by
spinal commissural axons. The critical feature of the model is that
commissural growth cones change their responses to these molecules at
the ventral midline, perhaps as a result of interactions with the floor
plate. Commissural growth cones extend ventrally on the ipsilateral side
of the cord because they are repulsed by Sema Z2 secreted by the roof
plate and attracted by Netrin-1a and Netrin-1b secreted by the ventral
half of the cord and floor plate, respectively; pause at the floor plate
to reprogram themselves; and then extend ventrally on the contralateral
side because they are insensitive to or attracted by Sema Z2,
insensitive to or repulsed by Netrin-1b, and insensitive to or remain
attracted to Netrin-1a. Furthermore, Sema Z7 which is now expressed by
the dorsal cord repulses the growth cones so that they now turn to
extend longitudinally in the dorsal cord. Our basic strategy will be
to manipulate semaphorins and netrins and determine how this affects the
behavior of growth cones in zebrafish embryos. In addition, we will
test the redundancy proposed in the model by examining commissural
growth cones in spinal cords missing both the roof and floor plate so
that they are devoid of molecules including Sema Z2 and Netrin-1b
derived from the roof and floor plate.
本提案将研究网状蛋白和信号素在轴突中的作用。
在斑马鱼中引导。信号素和netrins的发现
导致对化学吸引和排斥机制的欣赏
轴突引导。然而,我们对药物在体内作用的理解
这些分子仍然是不完整的。1.信号量是一个很大的
分子家族,但它们的功能只有3个已知
信号素。这项提案将研究另外2个在体内的作用。
信号素。2.显然,有几个机制是协同工作的
引导轴突。我们现在对个人如何
Netrins和信号素起作用,但还不知道这些分子是如何工作的
共同引导特定的生长锥体。这项提案将看到如何
这些分子协同工作,引导脊髓连合轴突。3.
连合生长锥首先向中线延伸,然后向外延伸。
从中枢神经系统的中线。他们是如何做到这一点的
两侧对称的引导提示,例如具有化学吸引力的netrins
在中枢神经系统腹侧中线的表达,目前还不清楚。
这项提案测试了一种解释这种行为的机制。
基于我们对斑马鱼中网状蛋白和信号素的分析
这些分子在其他生物体中的作用,一个结合了
生成了2个netrins和2个信号素,以说明通过
脊髓连合轴突。该模型的关键特征是
连合生长锥体改变它们对这些分子的反应
腹中线,可能是与地板相互作用的结果
盘子。连合生长锥体向同侧腹侧延伸
因为它们被屋顶分泌的Sema Z2排斥
被腹侧分泌的Netrin-1a和Netrin-1b所吸引
分别将绳索和地板的一半;暂停在地板上
重新编程;然后在对侧伸展腹肌
因为他们对Sema Z2不敏感或被Sema Z2吸引,
对Netrin-1b不敏感或排斥,对Netrin-1b不敏感或保持不变
被Netrin-1a所吸引。此外,SEMA Z7现在由以下表达式表示
背索排斥生长锥体,因此它们现在转向
在背部脊髓纵向伸展。我们的基本战略将是
操作信号素和netrins并确定这如何影响
斑马鱼胚胎生长锥体的行为。此外,我们还将
通过检查连结来测试模型中提出的冗余
脊髓中的生长锥缺少顶板和底板,因此
它们不含包括Sema Z2和Netrin-1b在内的分子
派生自屋顶和楼板。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('JOHN Y KUWADA', 18)}}的其他基金
Analysis of a Novel Regulator of Excitation-Contraction Coupling in Skeletal Musc
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- 批准号:
8927276 - 财政年份:2014
- 资助金额:
$ 25.38万 - 项目类别:
Analysis of a Novel Regulator of Excitation-Contraction Coupling in Skeletal Musc
骨骼肌兴奋-收缩耦合的新型调节器分析
- 批准号:
9041540 - 财政年份:2013
- 资助金额:
$ 25.38万 - 项目类别:
Analysis of a Novel Regulator of Excitation-Contraction Coupling in Skeletal Musc
骨骼肌兴奋-收缩耦合的新型调节器分析
- 批准号:
9251234 - 财政年份:2013
- 资助金额:
$ 25.38万 - 项目类别:
Analysis of a Novel Regulator of Excitation-Contraction Coupling in Skeletal Musc
骨骼肌兴奋-收缩耦合的新型调节器分析
- 批准号:
8503874 - 财政年份:2013
- 资助金额:
$ 25.38万 - 项目类别:
Genetic Analysis of Neuromuscular Junction Formation
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- 批准号:
7992358 - 财政年份:2009
- 资助金额:
$ 25.38万 - 项目类别:
Genetic Analysis of Neuromuscular Junction Formation
神经肌肉接头形成的遗传分析
- 批准号:
7580520 - 财政年份:2009
- 资助金额:
$ 25.38万 - 项目类别:
Genetic Analysis of Neuromuscular Junction Formation
神经肌肉接头形成的遗传分析
- 批准号:
8204505 - 财政年份:2009
- 资助金额:
$ 25.38万 - 项目类别:
Genetic Analysis of Neuromuscular Junction Formation
神经肌肉接头形成的遗传分析
- 批准号:
7789609 - 财政年份:2009
- 资助金额:
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