HORMONAL CONTROL OF CNS REORGANIZATION IN DROSOPHILA

果蝇中CNS重组的激素控制（PI，L.l. Restifo）拟议研究的重点是类固醇激素对中枢神经系统重塑的控制。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。黑腹果蝇模型系统中可用的遗传技术提供了这样一个机会。正在研究的假设是，类固醇激素20-羟基蜕皮激素（20 E）控制蘑菇体的重组，蘑菇体是学习和记忆所必需的大脑结构。在变态期间，由激素波动协调的发育间隔，蘑菇体结构通过轴突和树突的连续变性和再生以及神经发生和新生分化而改变。这种重塑很可能促进突触连接的建立，这对成年人特有的行为至关重要。凯尼恩细胞，在那里他们响应生理水平的20 E的增强神经突生长，与激素的体内作用一致。在体外反应是更大的女性和男性神经元，与成年女性大脑中的凯尼恩细胞轴突的数量较多。在野生型和突变体样品中，许多体外凯尼恩细胞特征与体内对应物相似。细胞培养和全脑实验的组合提出，以确定这三个凯尼恩细胞亚型是响应20 E，并确定这三个凯尼恩细胞亚型是响应20 E，并确定哪些调控基因的蜕皮激素级联神经突生长增强的基础。遗传性逆转实验将揭示20 E对神经突生长的性别作用是否将通过对表达绿色荧光蛋白的活培养蘑菇体神经元的连续观察来确定。Kenyon的形态和响应特性预测揭示了细胞缺陷，这些缺陷破坏了对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治疗和预防与异常神经元结构和功能相关的后天性和先天性疾病的新策略。

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.