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

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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.