FORMATION OF THE VISUAL CORTEX

细胞和分子底物与巨噬细胞死亡有关 发育中的视觉系统中的神经元数量仍然很少 特色化的。一种更独特的神经细胞群体 在亚板区发现发育中的细胞死亡，这是一种暂时性层 未成熟的大脑皮层。这一群体分化为一个 许多神经化学和形态上不同的类型形成了 视觉皮质和大脑皮质下的初始皮质内和皮质下投射 接受来自背侧的第一个功能性突触接触 膝状核。虽然这一现象的形成和消除 亚板块及其连接很可能具有主要的生物特征 了解大脑皮层发育机制的意义 在这个神经元群体中控制细胞死亡的事件在很大程度上是 未知。拟议研究的第一个目标是提供一个 详细描述了细胞和分子之间的相互作用 前和后的板下神经元、膝状体皮质和皮质轴突 在细胞死亡期间，使用亚板特异性分子标记 和抗神经营养因子和受体的抗血清 在光学和电子显微镜水平上的解剖学技术。 第二个目标是对一种新发现的 细胞周期中亚板细胞表达的抗原(SP1) 死亡及其调控，使用单抗，与 生化方法。第三个目标是定义细胞的类型 副本垒板上的死亡。这一目标将通过比较 自然发生神经元与自然发生神经元的分子特性比较 实验诱导的细胞死亡。这些研究将进一步推动我们的 对亚板在视皮层形成中作用的认识 以及这个结构中细胞死亡的原因。它们代表着重要的 确定早期和特异的细胞死亡标志物的第一步 无论是正常发育还是基因突变。新信息 Gain也可以为临床的发现提供合理的策略 预防与急性疾病相关的视力丧失的干预措施 导致神经元退化，如缺血、中风和创伤。

The cellular and molecular substrates associated with the death of massive numbers of neurons in the developing visual system remain poorly characterized. One of the more distinctive neuronal populations to undergo developmental cell death is found in the subplate zone, a transient layer of the immature cerebral cortex. This population differentiates into a number of neurochemically and morphologically distinct types which form the initial intra-cortical and subcortical projections of the visual cortex and receive the first functional synaptic contacts from the dorsal lateral geniculate nucleus. Although the formation and the elimination of the subplate and its connections are likely to be of major biological significance for understanding mechanisms of cortical development, the events controlling cell death in this neuronal population are largely unknown. The first objective of the proposed studies is to provide a detailed description of the cellular and molecular interactions between the subplate neurons and geniculocortical and corticocortical axons before and during the period of cell death, using subplate-specific molecular markers and antisera against neurotrophic factors and receptors, in conjunction with anatomical techniques at the light- and electron microscopic levels. The second objective is to biochemically characterize a newly-identified antigen (SP1) expressed by the subplate cells during the period of cell death and its regulation, using monoclonal antibodies, in combination with biochemical approaches. The third objective is to define the types of cell death in the subplate. This objective will be achieved by comparing molecular properties of neurons undergoing naturally-occurring versus experimentally-induced cell death. These studies will further our understanding of the role of the subplate in formation of the visual cortex and the causes of cell death in this structure. They represent important first steps in identifying the early and specific markers for cell death in both normal development and in genetic mutations. The new information gained could also provide a rational strategy for the discovery of clinical interventions to prevent vision loss associated with acute conditions causing neuronal degeneration, such as ischemia, stroke and trauma.