The molecular logic of synaptic wiring at the single cell level

Abstract

The correct wiring of neuronal circuits is one of the most complex processes in development, since axons form highly specific connections out of a vast number of possibilities. Circuit structure is genetically determined in vertebrates and invertebrates, but the mechanism guiding each axon to precisely innervate a unique pre-specified target cell is poorly understood. Here, we used single cell genomics, imaging and genetics to show that single-cell specific connections between motoneurons and target muscles are specified through a combinatorial code of immunoglobulin domain proteins. These programs are orchestrated by a homeodomain transcription factor code that specifies cellular identities down to the level of biologically unique cells. Using spatial mapping, we show that this code follows spatial patterns already observed at early embryonic stages, while acting at a much later stage to specify motor circuits. Taken together, our data suggest that a relatively simple homeo-immunoglobulin-code determines neuronal circuit structure.