Modeling Fragile X syndrome with iPSC-derived neurons as a purpose of deciphering the molecular mechanisms and the neurobiological phenotypes associated with the pathology.
Fragile X syndrome (FXS) is the most common inherited form of human mental retardation and it is caused by expansion of CGG repeat in the FMR1 gene. The resulting epigenetic silencing causes the loss of the fragile X mental retardation protein (FMRP) with defects in the regulation of dendritic spine morphology and synaptogenesis.
The aim of our study is to create an in vitro model based on human induced pluripotent stem cells (hiPSCs) with the purpose of deciphering the molecular mechanisms and the neurobiological phenotypes associated with FXS.
We developed a culture system for cortical neuron differentiation and we obtained TUJ1-positive cells to study electrophysiological properties and axon growth dynamics of FXS-iPSCs derived neurons.
Moreover, preliminary calcium imaging and patch clamp recordings suggested a good degree of maturation of these neurons, which form a connected and partially synchronized network. Therefore, the creation of a robust in vitro model based on hiPSCs can be used to study FXS in a time frame that is relevant to the disease, understand its mechanisms and allow for therapeutic testing, all in cells carrying the genetic background of individual patients.