department of developmental biology

Associate Professor

Department of Developmental Biology
Neurosciences Program
Developmental Biology Program
Molecular Genetics Program

Research Interests

The synapse is the fundamental unit of function in the nervous system.
Understanding how synapses form, how they grow throughout development, and
how their structure and function are molded by neuronal activity are central
questions in neurobiology. A satisfying explanation for how we learn,
remember, and think--and insights into how neurological and psychiatric
diseases disrupt these processes--will require a deep understanding of
synaptic development, function, and plasticity. To investigate the molecular
mechanisms that regulate the functional and morphological development of
synapses we combine genetic, neuroanatomical, and electrophysiological
studies in both Drosophila and the mouse.

To investigate processes that regulate synaptic strength we focus on two
questions--1) What mechanisms and molecules regulate the localization of
glutamate receptors to the postsynaptic density? and 2) What factors control
the filling of synaptic vesicles with glutamate, and do presynaptic changes
in vesicle content regulate the strength of synapses?

In our studies of the morphological development of synapses we focus on a
key negative regulator of synaptic growth, a protein called highwire in
Drosophila. In the absence of highwire there is dramatic overgrowth of
synapses and those synapses have impaired synaptic release. Highwire
functions as a ubiquitin ligase and we are currently using biochemical and
genetic techniques to characterize the synaptogenic signal pathways
regulated by highwire. In addition, we have identified a single homolog of
highwire in the mouse, termed Phr, that is highly expressed in the
developing brain. We have generated constitutive and conditional knock outs
of Phr and we are characterizing the function of Phr for the development,
maintenance, stability, and function of mammalian synapses.

DiAntonio Biosketch

Education and Training

• Associate Professor Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 2005-present
• Assistant Professor Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 1999-2005
• Postdoctoral Fellow University of California at Berkeley, Department of Molecular and Cell Biology, 1995-1999. Postdoctoral Advisor: Dr. Corey Goodman
• Ph.D. Stanford University School of Medicine, Department of Molecular and Cellular Physiology, 1989-1995. Thesis Advisor: Dr. Thomas Schwarz
• M.D. Stanford University School of Medicine, 1989-1995
• M. Phil. Cambridge University, Biochemistry, 1989
• A.B. Harvard University, Biochemistry and Molecular Biology, 1984-1988

Honors and Awards

• Keck Distinguished Young Scholar, 2002-2007
• McKnight Scholar Award, 2002-2004
• Sloan Research Fellow, 2001-2003
• Edward Mallinckrodt, Jr. Foundation Award, 2000-2003
• Whitehall Foundation Award, 2000-2003
• Howard Hughes Medical Institute, Faculty Development Award, 2000-2002
• McDonnell Center Grant, 2000-2001
• Burroughs Wellcome Career Award in the Biomedical Sciences, 1998-2003
• Helen Hay Whitney Fellow 1996-1998
• Damon Runyon-Walter Winchell Fellow, 1996
• Medical Scientist Training Program Fellow, 1989-1995
• Hershel Smith Harvard Scholarship, Harvard College, 1988
• Phi Beta Kappa, Harvard College, 1988

Selected Publications

Viquez, N.M., Li, C.R., Wairkar, Y.P., DiAntonio, A. (2006) The B’ PP2A regulatory subunit well-rounded regulates synaptic growth and cytoskeletal stability at the Drosophila neuromuscular junction. J. Neuroscience (in press).

Collins, C.A., Wairkar, Y.P., Johnson, S.L., and DiAntonio, A. (2006) Highwire restrains synaptic growth by attenuating a MAP kinase signal. Neuron 51: 57-69.

Daniels, R.W., Collins, C.A., Chen, K., Gelfand, M.V., Featherstone, D.E., and DiAntonio, A. (2006) A Single Vesicular Glutamate Transporter is Sufficient to Fill a Synaptic Vesicle. Neuron 49: 11-16.

Wu, C., Wairkar, Y.P., Collins, C.A., and DiAntonio, A. (2005) highwire function at the Drosophila neuromuscular junction: spatial, structural, and temporal requirements. J. Neuroscience 25: 9557-9566.

Daniels, R.W., Collins, C.A., Gelfand, M.V., Dant, J., Brooks, E.S., Krantz, D.E., and DiAntonio, A. (2004) Increased Expression of the Drosophila Vesicular Glutamate Transporter Leads to Excess Glutamate Release and a Compensatory Decrease in Quantal Content. J. Neuroscience 24: 10466-10474.

Marrus, S.B., and DiAntonio, A. (2004) Preferential localization of glutamate receptors opposite sites of high pre-synaptic release. Current Biology 14: 924-931.

Marrus, S.B., Portman, S.L., Allen, M.J.,  Moffat, K.G.,  and DiAntonio, A. (2004) Differential localization of glutamate receptor subunits at the Drosophila neuromuscular junction.  J. Neuroscience 24: 1406-1415.

DiAntonio, A., Haghighi, A.P., Portman, S.L., Lee J.D., Amaranto, A.M., and Goodman, C.S. (2001) Ubiquitination-dependent Mechanisms Regulate Synaptic Growth and Function. Nature 412: 449-452.

Contact Information

Aaron DiAntonio
Department of Molecular Biology and Pharmacology
Washington University School of Medicine
Campus Box 8103
660 South Euclid Avenue
St. Louis, MO 63110
(314) 362-9925
diantonio@wustl.edu

Developmental Biology Program Website

http://molecool.wustl.edu/DevBiol/