Axons from a distinct group of neurons make contact with dendritic trees of target neurons in clearly segregated and laminated patterns, thereby forming functional units for processing multiple inputs of information in the vertebrate central nervous system. Whether and how dendrites acquire lamina-specific properties corresponding to each pathway is not known. We show here that vertebrate-specific membrane-anchored members of the UNC-6/ netrin family, netrin-G1 and -G2, organize the lamina/pathwayspecific differentiation of dendrites. Netrin-G1 and -G2 distribute on axons of different pathways and specifically interact with receptors NGL-1 and -2, respectively. In the hippocampus, parietal cortex, and piriform cortex, NGL-1 is concentrated in the dendritic segments corresponding to the lamina-specific termination of netrin-G1-positive axons, and NGL-2 is concentrated in distinct dendritic segments corresponding to the termination of netrin-G2-positive axons. In netrin-G1-and -G2-deficient mice, in which axonal path-finding is normal, the segmental distribution of NGL-1 and -2 is selectively disrupted, and the individual receptors are diffused along the dendrites. These findings indicate that transneuronal interactions of netrin-Gs and their specific receptors provide a molecular basis for the axonal innervation-dependent mechanism of postsynaptic membrane organization, and provide insight into the formation of the laminar structure within the dendrites.cortical layer ͉ neuronal circuit ͉ protein-protein interaction O ne remarkable feature of the vertebrate central nervous system is its cortical laminar structure. In addition to the layered distribution of different types of neurons, distinct populations of axons originating from multiple brain areas innervate distinct laminae. In cases where distinct axons project to a single neuron, they synapse onto distinct subcellular compartments (dendrite, soma, and axon initial segment), and in many cases, restricted segments within target dendrites (1). In mammalian hippocampus, for example, extrinsic inputs from the entorhinal cortex (EC) terminate on distal parts of the hippocampal neuronal dendrites, whereas fibers of inter-or intrahippocampal projections terminate on the proximal parts of dendrites in a laminated manner with sharp boundaries (2). Such laminaspecific connectivity along a dendrite might be the structural basis for organized processing and integration of multiple inputs. Various axon guidance molecules are implicated in the laminaspecific targeting of axons (3).Despite the well characterized laminar organization of presynaptic fibers, little is known about the lamina-specific properties of dendrites. Some electrophysiologic and immunolocalization studies demonstrated that dendrites originating from the same neuron possess distinct properties depending on the site, such as different neurotransmitter receptor compositions (4, 5), voltage-gated channel densities (6), and synapse morphology (7). However, these experiments were performed with very limited ce...

Advances in mouse neural circuit genetics, brain atlases, and behavioral assays provide a powerful system for modeling the genetic basis of cognition and psychiatric disease. However, a critical limitation of this approach is how to achieve concordance of mouse neurobiology with the ultimate goal of understanding the human brain. Previously, the common marmoset has shown promise as a genetic model system toward the linking of mouse and human studies. However, the advent of marmoset transgenic approaches will require an understanding of developmental principles in marmoset compared to mouse. In this study, we used gene expression analysis in marmoset brain to pose a series of fundamental questions on cortical development and evolution for direct comparison to existing mouse brain atlas expression data. Most genes showed reliable conservation of expression between marmoset and mouse. However, certain markers had strikingly divergent expression patterns. The lateral geniculate nucleus and pulvinar in the thalamus showed diversification of genetic organization between marmoset and mouse, suggesting they share some similarity. In contrast, gene expression patterns in early visual cortical areas showed marmoset-specific expression. In prefrontal cortex, some markers labeled architectonic areas and layers distinct between mouse and marmoset. Core hippocampus was conserved, while afferent areas showed divergence. Together, these results indicate that existing cortical areas are genetically conserved between marmoset and mouse, while differences in areal parcellation, afferent diversification, and layer complexity are associated with specific genes. Collectively, we propose that gene expression patterns in marmoset brain reveal important clues to the principles underlying the molecular evolution of cortical and cognitive expansion.

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