How Do Cadherins Control Photoreceptor Connectivity?

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DESCRIPTION (provided by applicant): Neurons in the retina make remarkably precise connections with their synaptic targets. Indeed, such precision is a hallmark of neuronal connectivity in many parts of the brain. These synaptic patterns define the wiring diagram of the nervous system and determine, in part, how the brain computes. Many of these connections are genetically programmed to form in the absence of sensory input. However, the molecular mechanisms that underlie how the genome encodes information about these patterns of connections and applies this information to specify the targets of each individual neuron are poorly understood. The visual system of Drosophila presents a unique opportunity to use genetic techniques to determine how such mechanisms can control neuronal target selection. Photoreceptor cells, for example, make synaptic connections with a spatially invariant group of post-synaptic partners, and can do so in the absence of visual input. How can such a precise set of connections be genetically hard-wired? The proposed experiments examine these mechanisms in the context of one particular group of neuronal cell adhesion molecules, the cadherins. These proteins are thought to play critical roles in controlling synapse formation. How do classical cadherins influence synaptic partner choice? (Aim 1) How are the functions of classical cadherins regulated in neurons? (Aim 2) Do other cadherins also play a role in neuronal target selection? (Aim 3) Genetic disruptions in cadherin function cause inherited forms of retinitis pigmentosa, macular degeneration and defects in brain development. However, the molecular mechanisms that underlie cadherin functions in the brain are almost entirely unknown. Understanding these functions in a facile model system may suggest novel therapeutic strategies.