RUI: Development Analysis of Forebrain

9511042 Eagleson这项研究将调查脊椎动物早期的前脑发育。之所以选择使用这种动物，是因为在该物种中发现的一种突变直接影响前脑和眼睛的发育，而这种突变提供了一种消极的条件，从而扰乱了发育。使用正常和突变的生物体，将用荧光标记技术生成详细的前脑命运图。对突变胚胎和正常胚胎神经板大脑命运的比较将测试突变胚胎中特定的中线早期神经板组织是否存在缺陷，以及何时出现缺陷。利用原位杂交技术，将跟踪正常和突变胚胎中前脑特异基因表达的逐步变化。这些研究将测试是否在突变胚胎和正常胚胎中出现前脑特异基因表达的时间或数量的差异，以及基因表达事件是否与特定的前脑缺陷有关。其他研究将测试突变情况可能如何改变后来的轴突生长和神经连接。这些研究将通过对发育中的神经元中形成的一种蛋白质进行免疫细胞化学来跟踪正常和突变胚胎中轴突和突触的发育。这些研究将揭示单个突变基因如何导致缺陷，并在发育后期显现出来。此外，这些研究还将为进一步研究脊椎动物神经发育提供一个发育框架和模型。

9511042 Eagleson This research will investigate early forebrain development in the vertebrate. The animal to be used was chosen because a mutation found within this species directly affects forebrain and eye development, and this mutation provides a negative condition whereby development is disrupted. Using normal and mutant organisms, a detailed forebrain fate map will be produced with fluorescent labeling techniques. A comparison of the mutant and normal embryo neural plate brain fates will test whether, and when, specific midline early neural plate tissue is defective in the mutant embryos. Using in situ hybridization techniques, stage by stage gene expression changes in forebrain specific genes will be followed in normal and mutant embryos. These studies will test to see if differences in the timing or amount of forebrain specific gene expression occurs in mutant and normal embryos, and if gene expression events can be related to the specific forebrain defects. Additional studies will test how the mutant condition might alter later axon growth and neural connections. These studies will follow axon and synapse development in normal and mutant embryos by using immunocytochemistry for a protein that is formed in developing neurons. These studies will reveal how a single mutant gene can result in defects that manifest themselves much later in development. In addition these studies will provide a developmental framework and model for further studies investigating vertebrate neural development.