HORMONAL CONTROL OF CNS REORGANIZATION IN DROSOPHILA

果蝇中枢神经系统重组的激素控制

• 批准号: 6665763
• 负责人: LINDA L RESTIFO
• 金额: $ 23.19万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665763
• 关键词: Drosophilidae; arthropod genetics; cell population study; central nervous system; developmental genetics; developmental neurobiology; ecdysone; gender difference; genetic regulation; green fluorescent proteins; hormone regulation /control mechanism; immunocytochemistry; learning; memory; metamorphosis; molecular cloning; molecular psychobiology; morphometry; neuroanatomy; neurogenesis; neurons; protein structure function; synapses; tissue /cell culture; transcription factor; video microscopy

Hormonal control of CNS reorganization in Drosophila (PI, L.l. Restifo) The focus of the proposed research is the control of central nervous system remodeling by steroid hormones. Given their widespread impact on human neural development and function, it is imperative that we achieve a better understanding of their action at cellular and molecular levels. The genetic technology available in the Drosophila melanogaster model system provides such an opportunity. The hypothesis under investigation is that the steroid hormone 20-hydroxyecdysone (20E) controls the reorganization of the mushroom bodies, brain structures that are essential for learning and memory. During metamorphosis, a developmental interval orchestrated by hormonal fluctuations, mushroom body structure is modified by sequential degeneration and regeneration of axons and dendrites, as well as neurogenesis and do novo differentiation. This remodeling is likely to promote the establish of synaptic connections critical for adult-specific behaviors. Kenyon cells, where they respond to physiological levels of 20E by enhanced neurite outgrowth, consistent with an in vivo role of the hormone. The in vitro response is much greater in females and in male neurons, consistent with the larger number of Kenyon cell axons in adult female brains. In both wild-type and mutant samples, a number of Kenyon cell characteristics in vitro are similar to their in vivo counterparts. A combination of cell culture and whole-brain experiments are proposed to determine which of the three Kenyon cell subtypes is responsive to 20E, and to determine which of the three Kenyon cell subtypes is responsive to 20E, and to determine which regulatory genes of the ecdysone cascade underlie neurite outgrowth enhancement. Genetic sex reversal experiments will reveal whether the sex action of 20E on neurite outgrowth will be determined by serial observations of live cultured mushroom body neurons expressing Green Fluorescent Protein. The morphology and hormone-response properties of Kenyon predicted to reveal cellular defects that disrupt the development of functional circuitry critical to experience-dependent neural plasticity. Information obtained from these studies will produce the generation of new strategies for treating and preventing acquired and congenital disorders associated with abnormal neuronal structure and function.

果蝇（PI，L.L。restifo）中CNS重组的激素控制拟议研究的重点是控制中枢神经系统通过类固醇激素重塑。鉴于它们对人类神经发育和功能的广泛影响，我们必须更好地了解它们在细胞和分子水平上的作用。果蝇Melanogaster模型系统中可用的遗传技术提供了这样的机会。所研究的假设是类固醇激素20-羟基甲虫（20E）控制了蘑菇体的重组，这对于学习和记忆至关重要。在变形过程中，通过激素波动策划的发育间隔，蘑菇体结构通过轴突和树突的顺序变性和再生以及神经发生并进行Novo分化来改变蘑菇体的结构。这种重塑可能会促进建立对成人特定行为至关重要的突触连接。 Kenyon细胞通过增强的神经突生长对20E的生理水平反应，与激素的体内作用一致。在女性和雄性神经元中，体外反应要大得多，与成年雌性大脑中较大的肯尼因细胞轴突一致。在野生型和突变样品中，体外的许多肯尼因细胞特征都与它们的体内对应物相似。提出了细胞培养和全脑实验的组合，以确定三个肯尼因细胞亚型中的哪个对20E有响应，并确定三个肯尼亚细胞亚型中的哪个对20E有响应，并确定ecdysone cascade cascade cascade cascade cascace的哪些调节基因的神经神经突发产生的生长增强。遗传性逆转实验将揭示20E对神经突生长的性作用是否会通过表达绿色荧光蛋白的活蘑菇身体神经元的连续观察确定。肯尼恩的形态和激素反应特性预测会揭示细胞缺陷，破坏了与经验依赖性神经可塑性至关重要的功能电路的发展。从这些研究中获得的信息将产生与异常神经元结构和功能相关的可获得和先天性疾病的新策略。