Classic Cadherins Mediate Selective Intracortical Circuit Formation in the Mouse Neocortex

Understanding the molecular mechanisms underlying the formation of selective intracortical circuitry is one of the important questions in neuroscience research. "Barrel nets" are recently identified intracortical axonal trajectories derived from layer 2/3 neurons in layer 4 of the primary somatosensory (barrel) cortex. Axons of layer 2/3 neurons are preferentially distributed in the septal regions of layer 4 of the barrel cortex, where they show whisker-related patterns. Because cadherins have been viewed as potential candidates that mediate the formation of selective neuronal circuits, here we examined the role of cadherins in the formation of barrel nets. We disrupted the function of cadherins by expressing dominant-negative cadherin (dn-cadherin) using in utero electroporation and found that barrel nets were severely disrupted. Confocal microscopic analysis revealed that expression of dn-cadherin reduced the density of axons in septal regions in layer 4 of the barrel cortex. We also found that cadherins were important for the formation, rather than the maintenance, of barrel nets. Our results uncover an important role of cadherins in the formation of local intracortical circuitry in the neocortex.