Doublecortin (Dcx): a MAP for Migration in the Developing Brain

Funded Activity Summary

When a child is born with mental retardation or epilepsy, every parent wants to know why. There are many treatable causes, including poor nutrition, damage at birth and exposure to viruses or drugs. Other triggers for mental retardation and epilepsy are neither preventable nor treatable. Of the latter group, genetic diseases are one of the most important causes and are still not fully understood. At the Children's Medical Research Institute, we are involved in finding out how the brain develops normally so that we can come to understand how our genes can cause conditions such as mental retardation and epilepsy. In understanding the normal development of the brain, we have focused on a gene known as doublecortin (Dcx). Mutations in doublecortin result in both mental retardation and epilepsy in a condition known as lissencephaly (smooth brain). Children with lissencephaly have fewer nerve cells (neurons) within their brains when compared to others of the same age, a problem thought to arise before their birth. At this time, the neurons are formed deep within the brain and migrate from this starting point to a final resting place nearer to its surface. This migration fails in lissencephaly and suggests a very important role for doublecortin in normal migration and brain development. We intend to undertake biochemical approaches which will tell us Dcx function in neuronal cells and in animals which have had Dcx expression altered. Dcx is reported to interact with the cells scaffolding system (microtubules). We will investigate interactions of normal and modified Dcx with microtubules. Following on the neuronal cell studies, transgenic mice will be developed expressing normal and mutated Dcx which will allow in depth analysis of gene function in an in vivo system. Ultimately our studies will lead to an understanding of Dcx role in microtubule dynamics and its involvement in neuronal migration and lissencephaly.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $366,100.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Genetic Development (Incl. Sex Determination)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Brain Development | Doublecortin | Inherited Disorders | Lissencephaly | Mental Health, Epilepsy | Nervous System Disorders | Neuronal Migration | Subcortical Laminar Heterotopia | cortical Development

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