Cortical neurogenesis in fragile X syndrome

Abstract

The absence of fragile X mental retardation 1 protein (FMRP) results in fragile X syndrome (FXS) that is a common cause of intellectual disability and a variant of autism spectrum disorder. There is evidence that FMRP is involved in neurogenesis. FMRP is widely expressed throughout the embryonic brain development and its expression levels increases during neuronal differentiation. Cortical neural progenitors propagated from human fetal FXS brain show expression changes of genes which encode components of intracellular signal transduction cascades, including receptors, second messengers, and transduction factors. The absence of functional FMRP enhances transition of radial glia to intermediate progenitor cells. Radial glial cells provide scaffolding for migrating neurons and express functional receptors for metabotropic glutamate receptors. The absence of FMRP results in alterations of neuronal differentiation and migration, which contribute to developmental changes in brain structure and function in FXS. Here, cortical neurogenesis in FXS is reviewed and the putative contribution of brain-derived neurotrophic factor to defects of FXS neurogenesis is discussed.