Developmental patterns of cadherin expression and localization in relation to compartmentalized thalamocortical...

The wiring of synaptic circuitry during development is remarkably precise, but the molecular interactions that enable such precision remain largely to be defined. Cadherins are cell adhesion molecules hypothesized to play roles in axon growth and synaptic targeting during development. We previously showed that N-cadherin localizes to ventrobasal (VB) thalamocortical synapses in rat somatosensory (barrel) cortex during formation of the whisker-map in layer IV (Huntley and Benson [1999] J. Comp. Neurol. 407:453-471). Such specific association of N-cadherin with one identified afferent pathway raises the prediction that other cadherins are expressed in barrel cortex and that these are, in some combination, also differentially associated with distinct inputs. Here, we first show that N-cadherin and three other classic cadherins (cadherin-6, -8, and -10) are expressed contemporaneously in barrel cortex with relative levels of postnatal expression that are highest during the first 2 weeks, when afferent and intrinsic circuitries are forming and synaptogenesis is maximal. Each displayed distinct, but partly overlapping laminar patterns of expression that changed over time. Cadherin-8 probe hybridization formed a particularly striking pattern of intermittent, columnar patches extending from layer V through layer III, which was first detectable at approximately postnatal day 3. The patches were centered precisely over regions of dysgranular layer IV and, in the whisker barrel field, over barrel septa. This pattern is similar to that formed by the terminal distribution of thalamocortical afferents arising from the posterior nucleus (POm), suggesting cadherin-8 association with the POm thalamocortical synaptic circuit. Consistent with this, cadherin-8 mRNAs were enriched in the POm nucleus, and cadherin-8 immunolabeling in layer IV was enriched in barrel septa and codistributed with labeled POm thalamocortical synaptic-like puncta. The striking molecular parcellation of at least two different cadherins to the two, converging thalamic pathways that terminated in non-overlapping barrel center and septal compartments in layer IV strongly suggested that cadherins provide requisite molecular recognition and targeting that enable precise construction of thalamocortical and other synaptic circuitry.