The genetic network downstream of tcf mediated Wnt/beta-catenin signaling during the establishment of brain asymmetries

每个人都可以同时执行多项任务。这种多功能性的一个原因是左右脑半球的使用不同。这些功能不对称性与脑中的形态不对称性之间是否存在关联以及如何关联仍然是神经科学中的一个基本问题。为了理解多功能性背后的神经线路，我们需要阐明对其建立至关重要的遗传网络。只有这样，我们才能操纵网络的形成，并了解其功能的重要性。我们最近对斑马鱼高度保守和可接近的缰核神经回路的研究，导致了t细胞特异性因子（tcf）的鉴定。我们发现tcf介导的Wnt/β-catenin信号传导对于建立不对称连接非常重要，并且它可能与此过程中的另一个途径Notch途径相互作用。在两个平行的方法中，我们将联合收割机结合分子、遗传和成像技术来鉴定受tcf调控的分子。因此，我们的目标是找出tcf介导不对称神经回路发展的机制，特别关注它与Notch通路的相互作用。我们的分析将涉及正常和突变的斑马鱼窝藏多个转基因操纵基因功能和可视化的影响不对称的大脑发育在体内。我们预计，该项目的成果将产生很大的影响，因为从发育生物学家和神经科学家到医学研究人员的广泛读者将感兴趣。

Every human can perform several tasks simultaneously. One reason for this multifunctionality is that the left and right brain hemispheres are used differentially. How and if these functional asymmetries correlate with morphological asymmetries found in the brain is still a fundamental question in neuros-cience. To understand the neural wiring underlying multifunctionality we need to elucidate the genetic network important for their establishment. Only then we will be able to manipulate network formation and find out about its functional importance.Our recent investigations on the highly conserved and accessible habenula neural circuit in zebrafish have led to the identification of a t-cell specific factor (tcf). We found that tcf mediated Wnt/beta-catenin signaling is important to establish asymmetric wiring and that it may interact with another pathway in this process, the Notch pathway. In two parallel approaches we will combine molecular, genetic and imaging techniques to identify molecules that are regulated by tcf. Thereby we aim to find out about the mechanism by which tcf mediates asymmetric neural circuit development, with particular focus on its interplay with the Notch pathway. Our analysis will involve normal and mutant zebrafish harboring multiple transgenes to manipulate gene function and to visualise the effect on asymmetric brain development in vivo. We anticipate that the project’s outcome will be of high impact as a broad readership will be interested ranging from developmental biologists and neuroscientists to medical researchers.