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

Regulation of synapse elimination by FMRP  

This is an individual National Research Service Award for post-doctoral research training, which provides support for promising Fellowship Applicants with the potential to become productive, independent investigators in scientific health-related research fields. Proper elimination of synapses is critical for neuronal development and function, and dysregulation of synaptic function has been implicated in multiple developmental disorders, including fragile X syndrome (FXS). The proposed studies will investigate the role of specific proteins in regulating neuronal interactions in a mouse model of FXS, which is caused by loss-of-function mutations in the fragile X mental retardation protein (FMRP). FMRP may control synaptic function and be key in synaptic elimination. Potential upstream effectors of FMRP- dependent synapse elimination are unclear. However, recent data demonstrate that an activity-dependent transcription factor, myocyte enhancer factor 2 (MEF2), regulates synapse elimination in CA1 hippocampal neurons. Interestingly, MEF2 has been genetically linked to autism-spectrum disorders, including FXS. MEF2-regulated mRNA transcripts include cytoskeletal protein Arc, which is translated in response to activation of group I metabotropic glutamate receptors (mGluRs). Electrophysiology and transfection of neurons with mutant forms of FMRP will be used to determine which features of FMRP-dependent translation are necessary for MEF2-dependent synapse elimination, and similar techniques will be used to investigate the role of group I mGluRs and Arc in this process. These data may provide a molecular mechanism for the increased spine density in FXS and reveal deficits in MEF2-dependent function in the disease. The results of these experiments may lead to the development of new therapies for autism and mental retardation disorders. Project Status


Funder National Institutes of Health
Fiscal Year Funding $52,154.00
Current Award Period 2010-2012
Project Number 1F32HD062120-01A1
Principal Investigator Wilkerson, Julia
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? Federal
Institution University of Texas Southwestern Medical Center
State/Country Texas
Web Link 1 Regulation of synapse elimination by FMRP (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects N/A