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Interagency Autism Coordinating Committee (IACC)
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Project Element Element Description

Project Title

Project Title

Developmental in Axons underlie Neuropsychiatric Illness

Principal Investigator

Principal Investigator

Liu, Judy

Description

Description

Even though symptoms manifest later in life, neuropsychiatric disorders can arise from problems in development. Correct axonal growth and development is critical for formation of healthy neural circuitry and disorders such as schizophrenia, autism, and epilepsy are associated with abnormal axon tracts and may result from problems in axonal development. Our goal is to understand the cell biology behind axon development in an effort to elucidate the steps that may be disrupted in neuropsychiatric disease. We have shown that doublecortin Dcx), a causative gene for an early neurodevelopmental disorder, has a crucial role in axon guidance. We have recently identified two novel functions of Dcx, which are critical for understanding its function in how axons grow and find their final targets. 1) The N-terminal microtubule binding domains mediates the regulation of a subset of microtubule-based molecular motors. Molecular motors are proteins that facilitate transport within the cell, especially the long distance transport needed to maintain an axon. 2) The C-terminal domain appears to regulate the formation of actin polymers, so that in areas of high Dcx concentration, actin polymerization is stimulated. Thus, Dcx has effects on two type of the structural elements of the cell, or the cytoskeleton. These are called the actin and microtubule cytoskeleton. Based on our data, we hypothesize a role for Dcx in allowing signals that alter microtubule structure to be communicated to the actin cytoskeleton. Dcx may mediate 'cross-talk' between these domains. We propose that Dcx interaction with molecular motors and actin serves to dynamically coordinate vesicle trafficking between the MT and actin domains in developing growth cones. Our aims are to: 1) determine the role of Dcx-motor interactions in axonal development and 2) determine the role of Dcx-actin regulation in axonal development. This work will allow us to understand a novel mechanism in axon guidance, identify important interacting proteins to Dcx candidate genes for related diseases), and possibly define therapeutic targets for intervention.

Funder

Funder

Brain & Behavior Research Foundation

Fiscal Year Funding

Fiscal Year Funding

30000

Current Award Period

Current Award Period

2014-2016

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

Strategic Plan Objective

2O. Not specific to Question 2 objectives

Project Link

Project Link

No link available.

Institution

Institution

Children's Research Institute (CRI)

State/Country

State/Country

District of Columbia

Project Number

Project Number

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Developmental in Axons underlie Neuropsychiatric Illness | 30000 | 2014 |

 
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