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Title

 

University ID

3972

ShowOnHomePage

Yes

Full Name

 

First Name

Aaron

Last Name

DiAntonio

Degree

 

Faculty Keyword

axon, endocytosis, nerve regeneration, neurodegeneration, neuronal development and differentiation, synapse biology

Office Phone

314-362-9925

Lab Phone

314-362-9866

Other Phone

 

Fax

314-362-7058

Lab Address

333 McDonnell Medical Sciences Building

Email

 

Research Abstract

Our laboratory investigates molecular mechanisms that control the structure and function of neural circuits in development and disease. We combine genetic, molecular, neuroanatomical, and electrophysiological studies in both Drosophila and mouse to identify pathways required for the development and maintenance of axons and synapses. Our studies focus on three major areas:
 
1) Synaptic function: Neurotransmitter is released from the presynaptic cell at specialized sites called active zones. Efficient synaptic transmission requires that active zones contain a normal complement of proteins, and that these specialized release sites be apposed to postsynaptic clusters of neurotransmitter receptor. Little is known of the molecular mechanisms that regulate the protein composition of active zones and ensure the alignment of neurotransmitter release and reception machinery. Using large-scale genetic screens in Drosophila we are uncovering the molecular mechanisms that form and maintain the active zone/receptor cluster dyad.
 
2) Neural circuit formation and regeneration: 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. Highwire functions as a ubiquitin ligase and, using biochemical and genetic techniques, we are characterizing the synaptogenic signal pathways that it regulates. In addition, we have identified a single homolog of highwire in the mouse, termed Phr, which is highly expressed in the developing brain. We have generated constitutive and conditional knock-outs of Phr and we are characterizing it role in the formation, plasticity, and regeneration of neural circuits in the mammalian brain. These studies have also lead us to identify a novel membrane protein, Ema, that regulates endosome maturation.
 
3) Axonal degeneration in response to injury: Axonal degeneration is a common feature of many neurological diseases including hereditary neuropathies, diabetes, glaucoma, chemotherapy-induced neurotoxicity, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Axonal degeneration is an active process of self-destruction that appears to be naturally primed and waiting for a triggering stimulus that activates the execution phase. We have now identified the DLK/JNK MAP kinase pathway as the first intrinsic neuronal pathway that promotes axonal degeneration following injury. We are using molecular, genetic, and anatomical techniques in both Drosophila and mice to identify the molecular mechanisms driving axonal degeneration. Identifying and characterizing components of the intrinsic axonal degeneration pathway may identify potential therapeutic targets for the many neurological diseases characterized by axonal degeneration.

Middle Initial

 

Public Name

Aaron DiAntonio

Doctoral Degree1

 

Doctoral Degree2

 

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Division Primary Department

 

Campus Box

8103

Website Url

http://devbio.wustl.edu/Diantonionu.htm

Ten Word Res Desc

Neural circuits in development and disease

Micro Category1

 

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Date Last Updated

11/10/2011 11:18 AM

Publications

Shin JE and DiAntonio A.  Highwire regulates guidance of sister axons in the Drosophila mushroom body. J. Neuroscience 2011 (In Press).
 
Graf ER, Heerssen HM, Wright CM, Davis GW and DiAntonio A.  Stathmin is Required for Stability of the Drosophila Neuromuscular Junction. J. Neuroscience 2011 31: 15026-34.
 
Tian X, Li J, Valakh V, DiAntonio A and Wu C.  Drosophila Rae1 controls the abundance of the ubiquitin ligase Highwire in post-mitotic neurons. Nature Neuroscience 2011 14: 1267-75.
 
Daniels RW, Miller BR and DiAntonio A.  Increased Vesicular Glutamate Transporter Expression Causes Excitotoxic Neurodegeneration. Neurobiology of Disease 2011 41: 415-420.
 
Vohra BPS, Sasaki Y, Miller BR, Chang J, DiAntonio A and Milbrandt J.  Amyloid Precursor Protein Clevage-Dependent and –Independent Axonal Degeneration Programs Share a Common Nicotinamide Mononucleotide Adenylyltransferase Sensitive Pathway. J. Neuroscience 2010 30: 13729-13738.
 
Kim S, Wairkar YP, Daniels RW and DiAntonio A. The novel endosomal membrane protein Ema interacts with the class C Vps/HOPS complex to promote endosomal maturation. Journal of Cell Biology 2010 188: 717-734.
 
Graf ER, Daniels RW, Burgess RW, Schwarz T and DiAntonio A. Rab3 Dynamically Controls Protein Composition at Active Zones. Neuron 2009 64: 663-677.
 
Miller RB, Press C, Daniels RW, Sasaki Y, Milbrandt J and DiAntonio A. A DLK-dependent axon self-destruction program promotes Wallerian degeneration. Nature Neuroscience 2009 12: 387-389.
 
Wairkar YP, Toda H, Mochizuki H, Furukubo-Tokunaga K, Tomoda T, DiAntonio A. Unc-51 Controls Active Zone Density and Protein Composition by Downregulating ERK Signaling. J. Neuroscience 2009 29: 517-528.
 
Bloom AJ, Miller BR, Sanes JR and DiAntonio A. The requirement for Phr1 in CNS axon tract formation reveals the corticostriatal boundary as a choice point for cortical axons. Genes and Development 2007 21: 2593-2606.

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http://dbbs.wustl.edu/Faculty Photos Thumbnail/DiAntonio_A.jpg

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http://dbbs.wustl.edu/Faculty Photos/DiAntonio_A.jpg

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Research Image Description

 

Research Image Url

http://dbbs.wustl.edu/Faculty Research Images/Aaron_DiAntonio_3972.jpg

Social Media Url

 
Approval Status Approved
 

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Created at 11/10/2011 11:18 AM by DBBS_SP_SAPP
Last modified at 11/10/2011 1:19 PM by Kathryn Ruzicka