Many of the social and cognitive behavioral impairments associated with autism spectrum disorders (ASDs) are likely caused by changes in early brain development that alter the formation of neural circuits, and in particular, the neural circuitry of the cerebral cortex. Because early brain development is completed long before the onset of any identifiable behavioral changes, most studies of the developmental origins of autism have focused on animal models of genetic syndromes or rare single-gene mutations that lead to ASD-like behaviors. It is not clear how these different syndromes may be related to one another, or how these distinct genetic changes can each lead to similar behavioral outcomes.
Thomas Maynard and his colleagues at George Washington University are investigating whether 22q11.2 deletion syndrome, a genetic disorder associated with a high incidence of ASD, may be related to several other autism-related disorders that are known to disrupt a key signaling pathway focused on a protein called mTOR (mammalian target of rapamycin). The researchers plan to study mouse models of 22q11.2 deletion, where they have previously identified disruptions in the initial formation of cells in the cerebral cortex and in the migration of a subset of neurons that modulate brain activity1,2. The team will use targeted genetic approaches to ask whether mTOR is disrupted in 22q11.2 deletion, and whether altering mTOR signaling can prevent developmental anomalies in the cortex of the 22q11.2 deletion mouse model.
The researchers hypothesize that it is possible to identify similarities between these seemingly disparate genetic syndromes that cause ASD. By identifying shared or parallel mechanisms at the cellular or molecular level, it may be possible to more thoroughly understand which aspects of development are crucial to the onset of ASD, and possibly identify shared therapeutic approaches that may benefit individuals with ASD.
References:
1. Meechan D.W. et al. Proc. Natl. Acad. Sci. USA 106, 16434-16445 (2009) PubMed
2. Meechan D.W. et al. Proc. Natl. Acad. Sci. USA 109, 18601-18606 (2012) PubMed
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
