The L1 adhesion molecule normalizes neuritogenesis in Rett syndrome-derived neural precursor cells.
In this work we showed that ectopic expression of the L1 cell adhesion molecule could rescue some of the cellular phenotypes in Rett syndrome. This unusual link might be explored as a novel therapeutic opportunity.
Therapeutic intervention is an important need in ameliorating the severe consequences of Rett Syndrome (RTT), a neurological disorder caused by mutations in the X-linked gene methyl-CpG-binding protein-2 (MeCP2). Following previously observed morphological defects in induced pluripotent stem cell (iPSC)-derived neurons obtained from female RTT patients, we hypothesized transfection with the L1 cell adhesion molecule (L1) could contribute to normalizing a pathological male cell system bearing a nonsense mutation of MeCP2. We found a decreased expression of L1 in RTT iPSCs-derived neural precursor cells (RTT NPCs) and decreased neuritogenesis. Expression of wild-type MeCP2 in RTT NPCs revealed a positive correlation between the levels of MeCP2 and L1 and normalization of cell survival. Expression of L1 in RTT NPCs enhanced neuritogenesis and soma size. Knock-down of MeCP2 in wild type NPCs reduced neuritogenesis. L1 expression is regulated by the MeCP2 promoter. These results suggest that a deficiency in L1 may partially account for RTT phenotypes.