RUI: Development Analysis of Forebrain

这项研究将研究脊椎动物早期前脑的发育。之所以选择这种动物，是因为在这种动物身上发现的一种突变会直接影响前脑和眼睛的发育，这种突变提供了一种不利的条件，从而破坏了发育。使用正常和突变的生物体，详细的前脑命运图将产生与荧光标记技术。将突变胚胎与正常胚胎的神经板脑命运进行比较，将检验突变胚胎中特异性中线早期神经板组织是否以及何时存在缺陷。使用原位杂交技术，将在正常和突变胚胎中逐级跟踪前脑特异性基因的基因表达变化。这些研究将检验在突变胚胎和正常胚胎中，前脑特异性基因表达的时间或数量是否存在差异，以及基因表达事件是否与特定的前脑缺陷有关。进一步的研究将测试突变条件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形成的蛋白质进行免疫细胞化学，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在发育后期表现出来的缺陷。此外，这些研究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.