REGIONAL DIFFERENTIATION DURING FOREBRAIN DEVELOPMENT

该提案中的实验验证了这样一个假设： 哺乳动物端脑囊泡中的神经上皮区域 具有独特的细胞和分子特征， 囊泡分裂成主要亚部的雏形 前脑--新皮层，海马体，基底神经节， 嗅球和基底前脑 初步研究表明 小鼠端脑囊泡外侧壁的一个区域 在妊娠第10天和第12天之间被一致地识别 基于一些标准。 这里描述的实验将 确定这个区域是否真的是一个不起眼的胚胎区域 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， 神经突向内生长、细胞粘附和细胞运动。 这些实验 将使用DNA标记技术在胎鼠上进行， 神经元免疫细胞化学定位。特异性标记物和细胞 粘附分子以及荧光染料标记技术。 更多的实验将确定这个区域是否也是 其特征在于转录因子的独特表达， 维甲酸受体，可能参与差异基因 区内的表达。 已识别的 在发育早期投射到该区域的轴突群- 嗅觉轴突和侧区将被探索。 的假设 这些相互作用是由细胞的协调表达所引导的， 粘附分子，也许在一个共同的信号的控制下， 评估。 从这些实验中应该可以确定 神经上皮中的离散细胞群， 端脑可以在形态学上获得区域认同， 前脑的可区分的细分出现，无论这些 区域性差异对建立起始轴突具有重要意义 途径，以及是否表达发育调节 转录因子可能与这一过程相关。 如果这是 在这种情况下，可以得出结论，囊泡的初始分裂成 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房室性的机制 已知的过程在模式形成和区域 在胚胎发生的早期阶段分化。

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.