ANATOMY OF REGULATORY GENES IN FOREBRAIN DEVELOPMENT

研究建议：皮质发育取决于一系列细胞 涉及生长因子和神经递质的相互作用。 成人 在大脑中，这些分子诱导快速和瞬时表达 可能控制长期反应的蛋白质。 类比小说 调节基因，由突触活动诱导，高表达 水平，在关键时期，在发展中的皮层被确定在博士。 沃利的实验室通过分子克隆技术。 Adr-1编码一个45 与血影蛋白同源的kD蛋白，似乎是脑特异性的 并在关键的产后时期表达，这表明 细胞外刺激和神经元形态变化之间的联系。 Rasp 编码与ras（40%同一性）和rap具有同源性的GTP结合蛋白 (45%同一性）并且在产前大鼠皮质中表达。 像拉斯一样， rasp转化NIH 3 T3细胞，表明在细胞增殖中的积极作用。 信号装置. 核心假设是生理活动诱导了 adr-1和rasp的表达，并且还调节它们的细胞内 本地化 这将在目标1和目标2中在正常大鼠皮层中进行测试。 2，分别。 在得到这个基本框架之后， 将在两种动物模型中进行，其特征在于降低 皮质输入，与智力低下相关：患有 营养环境剥夺与基底前脑小鼠 新生儿病变（目标3和4）。 环境：考夫曼博士的活动将在环境的背景下， 精神发育迟滞中心，由几个研究小组组成 研究与智力迟钝有关的不同方面的发展 例如大脑发育中的基因表达。

Research proposal: Cortical development depends on a sequence of cellular interactions involving growth factors and neurotransmitters. In adult brain, these molecules induce the rapid and transient expression of proteins that may control long-term responses. Analogous novel regulatory genes, induced by synaptic activity and expressed at high levels, at critical periods, in developing cortex were identified in Dr. Worley's laboratory by molecular cloning techniques. Adr-1 encodes a 45 kD protein with homology to spectrin, that appears to be brain specific and expressed during the critical postnatal period, suggesting a link between extracellular stimuli and changes in neuronal morphology. Rasp encodes a GTP-binding protein with homology to ras (40% identity) and rap (45% identity) and is expressed in the prenatal rat cortex. Like ras, rasp transforms NIH3T3 cells, indicating an active role in cellular signalling. The central hypothesis is that physiological activity induces the expression of both adr-1 and rasp and also modulates their intracellular localization. This will be tested, in normal rat cortex, in Aims 1 and 2, respectively. After obtaining this basic framework, a similar study will be performed in two animal models, characterized by decreased cortical input, and relevant for mental retardation: rats with nutritional-environmental deprivation and mice with basal forebrain neonatal lesions (Aims 3 and 4). Environment: Dr. Kaufmann's activities will be in the context of the Mental Retardation Center, which comprises several research groups studying different aspects of development relevant to mental retardation such as gene expression in brain development.