Lauren Weiss and colleagues used a reverse pathway genetic approach, focused on the RAS/MAPK pathway, to show that gene-gene interactions contribute to autism.
Motor dysfunction is common in autism. The primary motor cortex (area M1) has been implicated in the manifestation of these symptoms. Stelios Smirnakis proposes to study M1 circuit function, particularly during motor skill learning, to elucidate mechanisms that underlie motor deficits in autism.
Autism is a complex disorder of many biological causes that results in characteristic behavioral symptoms. However, recent advances in the genetics of autism point to a constellation of genetic causes that converge on a subset of intracellular signaling pathways, including RAS-MAPK and PI3K/AKT, that may all contribute to autism, even if mutations in these pathways on their own may not be sufficient to cause the disorder.
One of the most common genetic causes of autism is the loss or duplication of a small region on human chromosome 16 known as 16p11.2. These genetic changes account for only about 1 percent of all cases of autism, but when present, they frequently result in the disorder.
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.
Stelios Smirnakis and his team at Baylor College of Medicine in Houston, Texas, worked to understand how genetic defects in autism lead to malfunction at the circuit level. Understanding the mechanism of circuit malfunction will help generate new hypotheses on how to intervene to promote recovery.