The brain consists of two main types of cells, neurons and glia. Although neurons have been extensively studied, the contribution of glial cells to autism is not well understood. To address this deficit in knowledge, Erik Ullian and his colleagues proposed to investigate the developmental profile and functional properties of a special type of glial cell called an oligodendrocyte (OC), a specialized cell that enwraps axons with an insulating sheath that is essential for proper brain function and the transmission of signals among brain regions.

The most prevalent genetic form of mental retardation, fragile X syndrome, is a single-gene disorder leading to loss of the RNA-binding protein FMRP. Loss of FMRP results in improper messenger RNA (mRNA) translation at synapses — the junctions between nerve cells — synaptic dysfunction, impaired cognitive function and autism-associated behaviors. To investigate the role of synaptic mRNA translation in normal synapse development, mRNAs and their functions need to be identified. While studies have examined the mRNA populations localized to synapses in rodent model systems, the identity of mRNAs at human synapses is unknown.

Duplication of a small segment of human chromosome 7 has been found in some children with autism. Lucy Osborne and her colleagues at the University of Toronto aim to understand the effects of duplication of this region, 7q11.23, on the growth and function of the brain. They plan to study this using a mouse model with a similar duplication.

Genetic alterations in the tuberous sclerosis complex (TSC) genes, key mediators of protein synthesis, are strongly associated with autism spectrum disorders. Peter Sims and his colleagues at Columbia University Medical Center have developed a novel strategy for cell-type-specific profiling of protein synthesis in the brain, combining ribosome profiling with computational tools.

Mutations in different types of chromatin regulators are associated with autism. In many cases, the mutation disrupts the expression of one copy of the gene or causes a reduction in the expression of the protein.

Findings from autism genetics and the study of animal models of autism suggest that some biochemical pathways are commonly affected in people with autism. The ERK signaling pathway is one such pathway. It mediates the transmission of signals from cell-surface receptors to the cytoplasm and nucleus of cells. ERK signaling regulates diverse cellular processes such as cell proliferation, differentiation and survival; and in the nervous system, it is involved in cognitive function and memory formation.

The human protocadherin (PCDH) gene clusters (PCDH-alpha, -beta and -gamma) encode a family of cell surface proteins that function in cell-to-cell interaction during the development of the brain. Distinct subsets of PCDH genes from all three clusters are randomly expressed in individual neurons, and this results in the generation of enormous single-cell PCDH diversity in neurons that are otherwise identical.

Autism is a heterogeneous brain disorder believed to have both genetic and environmental contributions. Epigenetic mechanisms, including modification of DNA and histones — proteins that store and organize DNA — allow an organism to respond to the environment through changes in gene expression. There is compelling evidence from human genetic association studies and animal models supporting a role for epigenetic dysregulation in autism. In particular, defects in MeCP2 protein function cause Rett syndrome. In this pilot study, Hongjun Song and his colleagues at Johns Hopkins University School of Medicine in Baltimore explored the role of DNA modifications in neuronal gene expression, plasticity, behavior and autism.

Deletions on chromosome 16 at the 16p11.2 region result in autism in a small portion of the general population. Major vault protein (MVP) is a gene within this region.

Mutation in many different genes has been found in individuals with autism, suggesting that there are many different ways to trigger the disorder. James Gusella and his colleagues previously found a number of autism genes whose normal function involves regulating the expression of other genes. This finding led them to consider that some effects of inactivating mutations in different autism genes might produce overlapping changes in overall gene expression. In this way, quite different genetic mutations might lead to autism by disrupting the same neurodevelopmental mechanisms.