Identification and localization of multiple classic cadherins in developing rat limbic system

Classic cadherins are multifunctional adhesion proteins that play roles in tissue histogenesis, neural differentiation, neurite outgrowth and synapse formation. Several lines of evidence suggest that classic cadherins may establish regional or laminar recognition cues by virtue of their differential expression and tight, and principally homophilic, cell adhesion. As a first step toward investigating the role this family plays in generating limbic system connectivity, we used RT-PCR to amplify type I and type II classic cadherins present in rat hippocampus during the principal period of synaptogenesis. We identified nine different cadherins, one of which, cadherin-9, is novel in hippocampus. Using in situ hybridization, we compared the cellular and regional distribution of five of the cadherins (N, 6, 8, 9 and 10) during the first two postnatal weeks in hippocampus, subiculum, entorhinal cortex, cingulate cortex, anterior thalamus, hypothalamus and amygdala. We find that each cadherin is differentially distributed in distinct, but highly overlapping fields that largely correspond to known anatomical boundaries and are often coordinately expressed in interconnected regions. For example, cadherin-6 expression defines CA1 and its principal target, the subiculum; cadherin-10 is differentially expressed in CA1 and CA3 in a manner correlating with the organization of interconnecting Schaffer collateral axons; and cadherin-9 shows a striking concentration in CA3. Some cadherin mRNAs are highly restricted to particular anatomical fields over the entire time course, while others are more broadly expressed and become concentrated within particular domains coincident with the timing of afferent ingrowth. Our data indicate that classic cadherins are sufficiently diverse and differentially distributed to support a role in cell surface recognition and adhesion during the formation of limbic system connectivity.