A crossroad of neuronal diversity to build circuitry.

One of the most important questions in brain science is how infinite information is processed and maintained by a finite number of neurons. A nearly limitless number of combinations and groups of neurons can be produced and connected with each other from a limited number of neurons. It is thought that a diversity of cell-surface proteins could form the basis of a molecular code for individual neuron identity (1). Considering the relatively small number of genes in the human genome (∼2 × 104), the explosive combination of different isoforms derived from each gene could contribute to such neuron diversification. In contrast to the diverse specific connections between neurons, brains also have diffuse neuronal projections that broadly regulate brain function. In this case, appropriate spacing of neurites (axon or dendrite projections of a neuron) is thought to be controlled by self-avoidance (repulsion between neurites belonging to an individual cell) and tiling (repulsion between neurites from different neurons of the same cell type) (2). On pages 406 and 411 of this issue, Chen et al. (3) and Mountoufaris et al. (4), respectively, provide mechanistic insights on specific and diffuse neuronal projections by focusing on clustered protocadherin (Pcdh) proteins, a group of cell adhesion molecules, using olfactory and serotonergic neural systems as models.