Developing neurons connect in specific and stereotyped ways to form the complex circuits that underlie brain function. By comparison to earlier steps in neural development, progress has been slow in identifying the cell surface recognition molecules that mediate these synaptic choices, but new high-throughput imaging, genetic, and molecular methods are accelerating progress. Over the past decade, numerous large and small gene families have been implicated in target recognition, including members of the immunoglobulin, cadherin, and leucine-rich repeat superfamilies. We review these advances and propose ways in which combinatorial use of multifunctional recognition molecules enables the complex neuron-neuron interactions that underlie synaptic specificity.
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