Primary Ciliary Deficits in the Dentate Gyrus of Fragile X Syndrome

Summary The primary cilium is the non-motile cilium present in most mammalian cell types and functions as an antenna for cells to sense signals. Ablating primary cilia in postnatal newborn neurons of the dentate gyrus (DG) results in both reduced dendritic arborization and synaptic strength, leading to hippocampal-dependent learning and memory deficits. Fragile X syndrome (FXS) is a common form of inheritance for intellectual disabilities with a high risk for autism spectrum disorders, and Fmr1 KO mice, a mouse model for FXS, demonstrate deficits in newborn neuron differentiation, dendritic morphology, and memory formation in the DG. Here, we found that the number of primary cilia in Fmr1 KO mice is reduced, specifically in the DG of the hippocampus. Moreover, this cilia loss was observed postnatally mainly in newborn neurons generated from the DG, implicating that these primary ciliary deficits may possibly contribute to the pathophysiology of FXS.
Graphical Abstract
Highlights • Primary cilia are significantly reduced in the DG of Fmr1 KO mice • Fmr1 KO mice show age-dependent primary cilia deficits • Neuronal ciliogenesis defects are shown in the DG of Fmr1 KO mice • Primary cilia deficits are observed in newborn neurons from SGZ, but not from DNe
In this article, Lee and colleagues show that Fmr1 KO mice, a mouse model for fragile X syndrome, have primary cilia deficits in the dentate gyrus (DG) found specifically in newborn neurons originating from the subgranular zone (SGZ) of the DG, but not in other hippocampal brain regions or from neurons originating from the dentate neuroepithelium (DNe).