REGIONAL DIFFERENTIATION DURING FOREBRAIN DEVELOPMENT

这个方案中的实验验证了不同的假设 哺乳动物端脑小泡的神经上皮区 具有独特的细胞和分子特征 囊泡的分裂成主要细部的雏形 前脑--新皮质、海马体、基底节、 嗅球和基底前脑。初步研究表明 小鼠端脑小泡侧壁的一个区域可以 在怀孕第10天和第12天之间被一致识别 基于一系列标准。这里描述的实验将 确定这个区域是否真的是一个谨慎的胚胎领域 这预示着前脑的区域分化。 首先，将评估该区域的独特细胞特征 通过检测细胞增殖、细胞周期、神经发生、 轴突向内生长、细胞黏附和细胞运动。这些实验 将使用DNA标记技术在胎鼠身上进行实验， 神经元的免疫细胞化学定位。特定的标记和细胞 粘合分子以及荧光染料标记技术。 其他实验将确定这一区域是否也 以转录因子的独特表达为特征的， 维甲酸受体，可能参与差异基因 在区域内表达。已确定的对象之间的特定交互 发育早期投射到该区域的轴突数量 嗅轴突--以及外侧区将被探索。假说 这些相互作用是由细胞的协调表达来引导的 黏附分子，可能在共同信号的控制下，将是 已评估。 从这些实验中，应该可以确定 人的神经上皮细胞中的一群离散的细胞 端脑可以在形态上之前获得区域认同 前脑的可区分的部分出现了，无论这些 区域差异对建立初始轴突具有重要意义 途径，以及表达是否受发育调节 转录因子可以与这一过程相关。如果这是 在这种情况下，可以得出结论，囊泡最初分裂成 结构和功能不同的前脑区域的雏形 依赖于类似于节段性和间隔性 已知的过程在格局形成和地区性 胚胎发育早期的分化。

The experiments in this proposal test the hypothesis that distinct regions of the neuroepithelium in the mammalian telencephalic vesicle have unique cellular and molecular characteristics prior to and during the division of the vesicle into rudiments of the major subdivisions of the forebrain-the neocortex, the hippocampus, the basal ganglia, the olfactory bulbs, and the basal forebrain. Preliminary studies suggest that a region in the lateral wall of the mouse telencephalic vesicle can be recognized consistently between the 10th and 12th day of gestation based upon a number of criteria. The experiments described here will determine whether or not this zone is truly a discreet embryonic domain that prefigures forebrain regional differentiation. Initially, the distinct cellular character of the zone will be assessed by examining differences in cell proliferation, cell cycle, neurogenesis, neurite ingrowth, cell adhesion and cell movement. These experiments will be performed on fetal mice using DNA labeling techniques, immunocytochemical localization of neuron. specific markers and cell adhesion molecules as well as fluorescent dye labeling techniques. Additional experiments will determine whether this zone is also characterized by the unique expression of a transcription factor, the retinoic acid receptor, that might be involved in differential gene expression within the zone. Specific interactions between an identified population of axons projecting to the zone early in development-the olfactory axons-and the lateral zone will be explored. The hypothesis that these interactions are guided by coordinated expression of cell adhesion molecules, perhaps under the control of a common signal, will be evaluated. From these experiments it should be possible to determine whether or not a discrete population of cells in the neuroepithelium of the telencephalon can acquire regional identity before morphologically distinguishable subdivisions of the forebrain emerge, whether these regional distinctions are significant for establishing initial axon pathways, and whether the expression of developmentally regulated transcription factors can be correlated with this process. If this is the case, one can conclude that the initial division of the vesicle into rudiments of structurally and functionally distinct forebrain regions relies upon mechanisms similar to the segmental and compartmental processes known to play a role in pattern formation and regional differentiation at earlier stages of embryogenesis.