Abstract

During the establishment of topographically organized connections in the nervous system graded distributions of axon guidance molecules play fundamental roles. In the retinotectal projection repulsive interactions of ephrins and Eph receptors guide the growth cones of retinal axons. However, it is still poorly understood how the growth cones read these gradients of membrane bound guidance molecules and convert this information into a meaningful cellular response. We use microcontact-printing and microfluidic networks to produce geometrically defined patterns of substrate bound ephrinA and EphA receptors to study axonal responses in a defined in vitro environment. I will first describe how retinal axons respond to microcontact printed gradients of ephrinA and how they read out this information with respect to gradient steepness and protein coating. In the second part I will provide experimental evidence that retinal growth cones are able to desensitize to this repulsive guidance factor and resensitize in response to ephrinA under certain conditions. Finally, I will present a theoretical model which implements all potentially relevant guidance cue interactions involved in the development of the retinotectal projection. The model is used to predict the outcomes of in-vitro assays of axonal guidance, which were then experimentally realized.