Identifying mRNAs associated with a synaptogenic calcium-mediated pathway

电压门控钙通道是驱动突触的引擎。它们是囊泡胞吐所必需的，现在很清楚，这些分子对神经网络变化的形成，维持，适应和消除的动力学至关重要。因此，当我们研究这些分子及其作用模式时，我们将对神经系统的基本组装有更清晰的了解。VGCC与人类疾病和障碍有关，我们的目标是进一步了解这些蛋白质如何促进神经元发育。使用具有使突触VGCC活化或过度活跃的突变的动物，我们将获得转录组谱以鉴定由VGCC功能状态转录调控的基因。然后，我们将针对这些基因进行RNAi敲除，以找到有助于VGCC依赖性突触添加的分子。最后，我们将寻求可视化钙可能是动态的时候，突触在发育过程中被修改相关的细胞内钙水平与特定的突触变化。C.线虫的神经肌肉系统为研究发育提供了强有力的遗传和细胞生物学模型。初级运动神经元与脊椎动物中枢神经系统神经元有许多相似之处，这更难以在体内研究。C. elegans可能提供重要的见解的机制，这些类型的突触的形成和间距在体内。

Voltage-gated calcium channels are the engines that drive the synapse. They are required for vesicle exocytosis, and it is now clear that these molecules are critically important to the dynamics of formation, maintenance, adaption and elimination that underlie changes in neural networks. Therefore, as we study these molecules and their mode of action, we will gain a much clearer understanding of the basic assembly of the nervous system. VGCCs have been linked to human diseases and disorders, and our goal is to further the understanding of how these proteins contribute to neuronal development. Using animals that have mutations that inactivate or hyperactive synaptic VGCCs we will obtain transcriptome profiles to identify genes that are transcriptionally regulated by VGCC functional status. We will then target those genes for knockdown by RNAi to find molecules that contribute to VGCC-dependent synapse addition. Finally we will seek to visualize how calcium may be dynamic during times when synapses are being modified during development to correlate intracellular levels of calcium with specific changes in synapses. The organization of the C. elegans neuromuscular system provides a powerful genetic and cell biological model to study development. The primary motorneurons have many similarities to vertebrate CNS neurons, which are more difficult to study in vivo. C. elegans may provide important insights into the mechanisms that underlie the formation and spacing of these types of synapses in vivo.