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.

L1 是一种含有免疫球蛋白结构域 (Ig) 的蛋白质，对于多种神经发育过程至关重要，并且在从蠕虫到人类的各个物种中高度保守。 L1 可以通过与其他含 Ig 的蛋白质结合来充当细胞粘附分子，或作为某些酪氨酸激酶受体（例如 FGFR 和 TRK）的配体，这些受体不仅在神经发育过程中而且在海马神经发生过程中都是必需的。然而，L1 本身在成人海马神经发生中的作用仍未得到解决。在这里，我们在小鼠中使用了多个 Cre 驱动程序系，有条件地删除了新神经元分化谱系的不同点以及海马成体齿状回周围神经元中的L1cam的 floxed 等位基因。我们发现干细胞/祖细胞中L1cam缺失增加了：1）祖细胞分化为新神经元，2）未成熟神经元中树突乔木的复杂性，3）焦虑相关行为。此外，神经元中L1cam的缺失会导致海马神经发生的年龄相关性提前下降。这些数据表明，L1 不仅对正常神经系统发育很重要，而且对维持成年后的某些神经过程也很重要。