Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and common comorbid condition in people with autism. Patients that suffer from FXS present with severe behavior phenotypes, including hyperactivity, impulsivity, anxiety, poor language development, and seizures. In FXS, the amplification of the trinucleotide CGG repeat element within the 5’ of the FMR1 gene on the X chromosome causes a fragile site at the q arm. The FMR1 gene product, FMRP, is an RNA binding protein involved in regulating many mRNAs in human excitatory and inhibitory neurons. FMRP is also involved in normal dendritic spine development, maturation, and synaptic formation. Dendritic spines are critical components for excitatory synaptic networks and important for neuronal communications. The lack of FMRP in neurons also leads to the dysregulation of microtubule formation. As a consequence of microtubule dysregulation, the formation of dendritic spines is negatively affected and compromised. While animal models of FXS have provided valuable insight into the neurobiology of this condition, recent clinical trials based on animal models have failed to correct disease-related phenotypes in patients with FXS. These discrepant impacts of the loss of FMR1 function in mouse versus human brain and mouse versus human embryonic stem cells could be attributed to interspecies differences in brain development. In this project, we will test the hypothesis that iPSCs-derived cortical neurons harboring Xq27-q28 deletion exhibit a significant decrease in axonal complexity, dendritic arborization, and networking.