Novel approaches for dissecting the function of neuronal receptor complexes in axonal and dendritic growth.

Brain function requires the establishment of precise neuronal networks connecting billions of neurons in a highly ordered fashion. A large part of this network is getting connected during embryonic development. Dendrite and axonal branching have important functional roles in determining how electrical signals are received by neurons and how they are processed. Much of the investigations on neural development and wiring in vertebrates have been conducted using the mouse as the key model organism. Recent advances in genome engineering offer now the opportunity to greatly expand the use of genetic approaches and generate knock-out as well as knock-in mutant frogs. We will apply these new technologies to characterize the roles of vertebrate DSCAM, DSCAML1 and receptor tyrosine phosphatases (RPTPs) in branching and patterning of axons and dendrites. We will test the hypothesis that during the “sprouting state” of an axonal growth cone DSCAMcontaining multi-receptor complexes are integrators of positive/negative cues and instrumental in selecting number as well as differential growth of axonal branches. Investigating the function of these receptors in transparent frog embryos and tadpoles promises to offer mechanistic insights at single cell resolution. We anticipate that this may provide new experimental paradigms to greatly facilitate medically relevant research in the area of neuronal wiring.