Neural cell adhesion molecule (
NCAM) is a membrane-bound cell recognition molecule that exerts important functions in normal neurodevelopment including cell migration, neurite outgrowth, axon fasciculation, and synaptic plasticity. Alternative splicing of
NCAM mRNA generates three main
protein isoforms: NCAM-180, -140, and -120. Ectodomain shedding of
NCAM isoforms can produce an extracellular 105-115 kilodalton soluble
neural cell adhesion molecule fragment (
NCAM-EC) and a smaller intracellular cytoplasmic fragment (
NCAM-IC).
NCAM also undergoes a unique post-translational modification in brain by the addition of
polysialic acid (
PSA)-NCAM. Interestingly, both
PSA-NCAM and
NCAM-EC have been implicated in the pathophysiology of
schizophrenia. The developmental expression patterns of the main
NCAM isoforms and
PSA-NCAM have been described in rodent brain, but no studies have examined
NCAM expression across human cortical development. Western blotting was used to quantify
NCAM in human postmortem prefrontal cortex in 42 individuals ranging in age from mid-gestation to early adulthood. Each
NCAM isoform (NCAM-180, -140, and -120), post-translational modification (
PSA-NCAM) and cleavage fragment (
NCAM-EC and
NCAM-IC) demonstrated developmental regulation in frontal cortex. NCAM-180, -140, and -120, as well as
PSA-NCAM, and
NCAM-IC all showed strong developmental regulation during fetal and early postnatal ages, consistent with their identified roles in axon growth and plasticity.
NCAM-EC demonstrated a more gradual increase from the early postnatal period to reach a plateau by early adolescence, potentially implicating involvement in later developmental processes. In summary, this study implicates the major
NCAM isoforms,
PSA-NCAM and proteolytically cleaved
NCAM in pre- and postnatal development of the human prefrontal cortex. These data provide new insights on human cortical development and also provide a basis for how altered
NCAM signaling during specific developmental intervals could affect synaptic connectivity and circuit formation, and thereby contribute to
neurodevelopmental disorders.