Project 4:
Understanding the genetic basis for mental retardation and autism.
The formation of the brain involves the production of many different kinds of neurons that must be positioned very precisely so that they can contact other neurons and integrate into functional neuronal circuits. New neurons are always generated at a distance from their final locations and they must travel along very specific routes in the developing brain to reach these locations (Heng et al, 2009 and see Figure 1). This process of neuronal migration is of considerable importance for the correct development of the brain, since mutations in genes that cause migration defects in the cerebral cortex during fetal life often result in severe mental retardation.
How does abnormal brain development result in mental retardation and epilepsy? This project will address the underlying genetic causes of neurological disorders such as mental retardation and epilepsy. We employ functional approaches (see Figure 2) to study key disease-causing genes for their role during brain development in vivo as well as in vitro (Figure 3). Recently, we identified a novel gene known as Rnd2 which is involved in the control of migration by newborn cortical neurons (Heng et al, Nature, 2008). Part of our continuing focus is to understand how this gene contributes to brain development, along with several other candidates known to be alleles for brain disease.
Publications
Heng, JI, Moonen, G., Nguyen, L. Neurotransmitters regulate cell migration in the telencephalon. European Journal of Neuroscience. 2007 Aug;26(3):537-46.
Heng, JI, Nguyen, L.,Castro, D., Zimmer, C., Armant, O., Skowronska-Krawczyk, D., Bedogni, F., Matter, J-M., Hevner, R., Guillemot, F. Neurogenin 2 controls cortical neuron migration through regulation of Rnd2. Nature. 2008 Sep 4;455(7209):114-8.
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