Two central challenges in autism research are defining specific neuronal abnormalities from genetic and environmental contributions and establishing preclinical models with human cells to test potential therapies. Autism is believed to be a disorder of neurodevelopment with a strong genetic liability. A large number of genetic risk loci have been identified by genetic association studies. Various animal models are being developed to explore the function of these genes in regulating neuronal development.

Human induced pluripotent stem (iPS) cells from patients provide an unlimited, stable and genetically tractable source of human cells. Studying the behavior of these cells could unlock a deeper understanding of the molecular and cellular mechanisms of complex human disorders such as autism, potentially leading to preclinical drug discovery and the development of cell replacement therapy.

Hongjun Song and his colleagues at Johns Hopkins University School of Medicine in Baltimore have generated iPS cells from individuals with autism who have specific genetic mutations. The group has developed novel approaches to use these iPS cells to explore defects in the development of human neurons.

In the nervous system, cells do not develop in isolation. Instead, cells’ properties are dynamically influenced by neighboring cells through direct interaction, by factors that come from more distant sources, and by electrical signals. Song and his colleagues established an in vivo model by transplanting a small number of neural stem cells (differentiated from iPS cells) into the developing rodent brain to examine the development of human neurons in a functional and intact neural environment.

This new model complements and extends the power of in vitro analysis to form a comprehensive picture of neural development, from neuronal migration and axonal targeting to the specificity and function of synapses, the junctions between neurons. The researchers hope this new model can be used to study different iPS cells derived from patients with various neurodevelopmental disorders.