L1cam curbs the differentiation of adult-born hippocampal neurons.

L1 is an immunoglobulin domain (Ig)-containing protein essential for a wide range of neurodevelopmental processes highly conserved across species from worms to humans. L1 can act as a cell adhesion molecule by binding to other Ig-containing proteins or as a ligand for certain tyrosine kinase receptors such as FGFRs and TRKs, which are required not only during neurodevelopment but also in hippocampal neurogenesis. Yet, the role of L1 itself in adult hippocampal neurogenesis remains unaddressed. Here, we used several Cre-driver lines in mice to conditionally delete a floxed allele of L1cam at different points along the differentiation lineage of new neurons and in surrounding neurons in the adult dentate gyrus of the hippocampus. We found that L1cam deletion in stem/progenitor cells increased: 1) the differentiation of progenitors into new neurons, 2) the complexity of dendritic arbors in immature neurons, and 3) anxiety-related behavior. In addition, deletion of L1cam in neurons leads to an earlier age-related decline in hippocampal neurogenesis. These data suggest that L1 is not only important for normal nervous system development, but also for maintaining certain neural processes in adulthood.