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The Drosophila gene turtle regulates class specific dendrite morphogenesis and larval locomotion.

机译:果蝇基因龟调节类特异性树突形态发生和幼虫运动。

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摘要

As the primary site for synaptic input and signal integration, neuronal dendrites perform a fundamental role in all functions of the nervous system including sensory perception, motor control, and learning and memory. Molecular insight into the mechanisms mediating dendrite morphogenesis is key for advancing our knowledge of these remarkable structures as well as for understanding the pathologies of nervous system diseases and aging. As the shape of a neuron's dendrites largely determines its function, studies of dendrite morphogenesis are critical for understanding neural circuit assembly and more globally nervous system activity. To elucidate the molecular bases underlying dendrite development, the dendritic arborization (da) neurons of the Drosophila melanogaster peripheral nervous system were used as a model system.;This thesis presents evidence that the conserved immunoglobulin superfamily (IgSF) member turtle (tutl) is required for class specific dendritic morphogenesis. Immunohistochemistry analyses revealed punctate expression of Tutl protein in da neuron cell bodies and dendrites. Loss-of-function experiments revealed that in morphologically complex neurons, tutl is required for promoting proper dendritic elaboration and receptive field coverage via effects on overall dendritic growth, whereas in morphologically simpler neurons, tutl primarily effects dendritic branching. In contrast to the tutl LOF analyses, overexpression of tutl in each class of da neuron did not produce any significant phenotypic changes. The homeodomain transcription factor Cut was shown to positively regulate tutl expression in da neurons. Finally, behavioral analyses indicate tutl is required for mediating normal larval locomotion.;Collectively, these studies reveal tutl as a novel regulator of class specific dendrite morphogenesis. The class-specific functions of tutl provide important information about the different molecular processes at work in various neuron subtypes. The regulatory interaction between cut and tutl represent the beginnings of understanding a new pathway regulating the acquisition of class-specific neuronal characteristics. Moreover, given the functional conservation between Drosophila and vertebrates for genes such as turtle and cut , (Shi et al., 2004a; Lemieux et al., 1994; Grueber et al., 2003), these studies may provide intriguing entry points for extending the findings obtained in Drosophila via model system studies in vertebrates.
机译:作为突触输入和信号整合的主要部位,神经元树突在神经系统的所有功能(包括感觉感知,运动控制以及学习和记忆)中起着基本作用。对介导树突形态发生机理的分子了解是提高我们对这些显着结构的认识以及理解神经系统疾病和衰老的病理学的关键。由于神经元树突的形状在很大程度上决定了神经元的功能,对树突形态发生的研究对于理解神经回路装配和更全面的神经系统活动至关重要。为了阐明树突发育的分子基础,以果蝇外周神经系统的树突状树突(da)神经元为模型系统。本论文提供了证据,证明需要保守的免疫球蛋白超家族(IgSF)成员乌龟(tutl)。用于类特异性树突形态发生。免疫组织化学分析显示,Tutl蛋白在da神经元细胞体和树突中呈点状表达。功能丧失实验表明,在形态复杂的神经元中,tutl是通过影响整体树突生长来促进适当的树突状细化和接受性区域覆盖所必需的,而在形态简单的神经元中,tutl主要影响树突状分支。与tutl LOF分析相反,在每类da神经元中tutl的过表达均未产生任何明显的表型变化。同源域转录因子Cut显示出正调控datl神经元中的tutl表达。最后,行为分析表明,tutl是介导正常幼虫运动所必需的。集体,这些研究表明,tutl是类特定树突形态发生的新型调节剂。 tutl的特定于类的功能提供了有关各种神经元亚型的不同分子过程的重要信息。 cut和tutl之间的调节相互作用代表了了解新的调节类特定神经元特征获取途径的开始。此外,鉴于果蝇和脊椎动物之间对诸如乌龟和割肉等基因的功能保守性(Shi等人,2004a; Lemieux等人,1994; Grueber等人,2003),这些研究可能为扩展提供了有趣的切入点。通过果蝇模型系统研究在果蝇中获得的发现。

著录项

  • 作者

    Sulkowski, Mikolaj J.;

  • 作者单位

    George Mason University.;

  • 授予单位 George Mason University.;
  • 学科 Biology Molecular.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 160 p.
  • 总页数 160
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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