Dendritic cell factor 1 deletion leads to developmental defects in mushroom-shaped dendritic spines.

Dendritic spines are divided into four subtypes, namely, Mushroom, Stubby, Thin, and Branched. The mushroom-shaped spines are related to learning and memory. Previous studies have shown that the dendritic cell factor 1 (Dcf1, a transmembrane protein) affects the memory process and regulates the development of dendritic spines by inhibiting the expression of lipocalin 2 (Lcn2, a member of the family containing over 20 small secreted proteins). However, the exact subtype of dendritic spines that are specifically affected by Dcf1 remains unknown. Here, we identified that deletion of Dcf1 leads to developmental defects in mushroom-shaped spines. We provide evidence for memory defects caused by Dcf1-knockout in mice. We discovered and report for the first time that Dcf1 affects the development of mushroom-shaped spines by inhibiting the expression of Lcn2. Further, we demonstrated that environmental enrichment can effectively stimulate Dcf1-knockout mice and rescue development defects in mushroom-shaped spines caused by Dcf1 deletion. Our results provide a novel direction for further studies on dendritic spine development and mechanisms associated with learning and memory.