Early and Late Development of Notch3 in Human Brains

Abstract

Notch1, 2, and 3, cell surface proteins, exhibit distinct spatial and temporal expression in a variety of regions in the developing brain, and the mutation of Notch3 is the cause of a hereditary disease, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). Notch system has been thought to have important functions during early neural development, but its function and significance in the developing central nervous system remain elusive. We demonstrated early and temporal Notch3 expression in progenitors of neurons and glial cells at an early fetal stage, and late and increasing Notch3 expression until adulthood in the vessels of human brains. This persistent Notch3 expression might influence the pathogenesis of CADASIL. Notch3 expression at a temporally early stage of neurons and glial cells, and in a period of permanent vessel development suggests the different and important roles of this protein during human brain development. Additionally, abnormal expression of Notch3 was detected in cortical neurons of type 2 lissencephaly and tuberous sclerosis brains. These data suggest that Notch3 might be a marker of delayed or abnormal maturation of neurons associated with migration and maturation disorders.