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Projects

Linking molecules to neural circuit function - the habenula in disease and brain asymmetry

The habenular neural circuit is part of everyone's brain. Whatever we see, smell or sense otherwise is at least partially worked on in this structure and relayed to other centers of the brain. If something does not work properly may have consequences on our mood, our sleep or social behavior. This can go really wrong and result in depression, schizophrenia or autism. Alongside the structure also various molecules, so called risk factors, have been discovered to underly such syndromes. However, the links between molecule and structure is frequently missing. We have uncovered molecules of the Wnt signaling cascade influencing the development and function of the habenula and have at the same time be linked to the mentioned diseases. One line of our research is following up these investigations.

 

The habenulae are clusters of neuronal cells, which are formed on both brain hemispheres (the red areas of the stained brains in the background). Like so many other areas of our brain, the habenulae are different and size and function between left and right. In our research group we would like to understand why there is this left-right asymmetry. Does this have something to do with performance? Would we behave differently if our brain would be more symmetric? Does symmetry equal disease syndromes?

To understand some of these questions we use fish as an in vivo model system, because for obvious reasons we can not manipulate a human brain to study the functional consequences. Our past research allowed us to understand more about how the habenular neurons develop on the genetic level and how the long axons they generate to connect to other brain centers find their way. Our aims are therefore two-fold: We aim to better help humans with habenula function related diseases like those mentioned. Further, we want to compare the behavior of fish with left-right symmetric and asymmetric brains and learn why asymmetry is so important. 

Axis Formation -

How come we have a head and legs? 

When we are nothing more than a cluster of cells shortly after sperm and egg have met, processes happen in the mother's womb that determine no less than whether we have a head or not (amongst many other things...). Like for determining left-right brain asymmetries above, one genetic pathway has turned out to be particularly important, Wnt signaling. We are taking a comparative genetics approach to find out which Wnt-related events during axis formation of the vertebrate embryo are evolutionarily conserved and which are species specific. Zebrafish and Medakafish share their last common ancestor about 150 Mio years ago, develop similarly and look comparable in size and shape. Intriguingly, our ongoing research suggests that the early processes of their development differ in critical aspects shedding new light onto the evolution of axis formation.

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