Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

Coordinated control of synapse development by autism-linked genes  

The development of brain cell connections, or synapses, in humans occurs during the third trimester of prenatal life and throughout the first few years of life. Proper synaptic formation and brain wiring requires a complex interaction between brain activity, usually driven by sensory experience, and genes. Many of the genes whose mutations are linked to autism play a role in synapse formation or pruning during brain development. Some people with autism show an excess of synapses, consistent with a deficit in synaptic pruning. Synaptic pruning is a normal developmental process that results in the elimination of inappropriate or unused synapses. Kim Huber and her colleague Chris Cowan have identified several genes that are required for proper synaptic pruning in the normal brain and that have links to autism. In response to brain activity, MEF2 triggers activation of a number of genes that lead to synapse elimination. The researchers also found that the gene linked to fragile X syndrome, FMR1, is required for MEF2 to cause pruning. FMR1 is a well-known autism risk gene that plays a role in converting MEF2-activated genes into proteins. MEF2 activates protocadherin 10, or PCDH10, whose deletion is associated with autism. Huber's team has found that PCDH10 is regulated by FMR1 and is required for synaptic pruning. The researchers hypothesize that a deficit in MEF2-mediated pruning contributes to autism. They plan to test whether the brains of mice lacking MEF2 have more synapses than normal, as observed in individuals with autism. They also plan to assess autism-related behaviors in these mice. Project Status


Funder Simons Foundation
Fiscal Year Funding $150,000.00
Current Award Period 2009-2011
Project Number 137345
Principal Investigator Huber, Kimberly
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Molecular Pathways
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 2SD. Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g. Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. IACC Recommended Budget: $9,000,000 over 5 years.
Federal or Private? Private
Institution University of Texas Southwestern Medical Center
State/Country Texas
Web Link 1 Coordinated control of synapse development by autism-linked genes (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects Coordinated control of synapse development by autism-linked genes | $75,000.00 | 2009 | 137345
Coordinated control of synapse development by autism-linked genes | $75,000.00 | 2011 | 137345
Coordinated control of synapse development by autism-linked genes | $0.00 | 2012 | 137345