Postnatal Microcephaly in MASA/CRASH Syndrome: L1 Cellular Adhesion Molecule Loss Leads to Smaller, Fewer, and Directionally Challenged Neurites

Abstract

Postnatal microcephaly in MASA/CRASH (mental retardation, aphasia, shuffling gate, adducted thumbs) syndrome is caused by compromised neurite outgrowth, arborization, and directionality. Neurite outgrowth is lost due to a lack of L1-cellular adhesion molecule (L1CAM, or L1) and ankyrins B and G interaction. Neurite arborization is compromised due to a loss of L1CAM and ezrin-radixin-moesin (ERM) protein interaction. L1CAM and neuropilin-1(NP1) interaction leads to a loss of neurite directionality. How these neurite growth changes affect neurogenesis throughout the brain, and lead to microcephaly (MiC), has not yet been modeled. Future drug discovery projects aiming to halt the progression of postnatal MiC in MASA syndrome could narrow the scope of focus if modeling software parameters were adjusted to reflect phenotypic changes to neurites lacking L1 demonstrated in the literature.