Research Awards
Janine LaSalle, Ph.D.
University of California Davis
The Role of MeCP2 in the Ontogeny of Cerebral Cortical Neurons
$50,000 (1 yr extension of existing award)
Lay Progress Report (August 2005)
Rett syndrome is cause by mutations in the gene MECP2 that encodes a protein, methyl-CpG protein 2 (MeCP2). Elevated MeCP2 expression is acquired in individual neurons within the brain beginning in infancy and progressing throughout childhood. The function of MeCP2 in the developing brain is unclear at this stage, but the mutations in Rett syndrome and the Mecp2 deficient mouse model provide evidence that MeCP2 is essential for mature neuronal function. MeCP2 is predicted to be a regulator of other genes in maturing neurons, but finding these genes is complicated by the complexity of cells and genes in the brain. This proposal used a cell culture system for inducing neuronal maturation to identify genes expressed in a single cell type at a precise time. MeCP2 activity was blocked by using a "decoy" inserted into the cells. Using this approach, a family of genes called the "ID" for "Inhibitors of Differentiation" were identified. The ID genes normally inhibit differentiation of cells, including neurons. The ID gene family showed abnormally high expression in the Mecp2 deficient mouse model and in Rett syndrome postmortem brain. These results suggest that increased expression of the ID genes may inhibit normal neuronal maturation, resulting in immature neurons and abnormal brain development in the Rett brain. These results could have relevance for future Rett treatments, as ID inhibitor drugs are currently being designed for potential cancer treatments.
Janine LaSalle, Ph.D.University of California Davis
The Role of MeCP2 in the Ontogeny of Cerebral Cortical Neurons
$50,000 (1 yr extension of existing award)
Lay Progress Report (August 2005)
Rett syndrome is cause by mutations in the gene MECP2 that encodes a protein, methyl-CpG protein 2 (MeCP2). Elevated MeCP2 expression is acquired in individual neurons within the brain beginning in infancy and progressing throughout childhood. The function of MeCP2 in the developing brain is unclear at this stage, but the mutations in Rett syndrome and the Mecp2 deficient mouse model provide evidence that MeCP2 is essential for mature neuronal function. MeCP2 is predicted to be a regulator of other genes in maturing neurons, but finding these genes is complicated by the complexity of cells and genes in the brain. This proposal used a cell culture system for inducing neuronal maturation to identify genes expressed in a single cell type at a precise time. MeCP2 activity was blocked by using a "decoy" inserted into the cells. Using this approach, a family of genes called the "ID" for "Inhibitors of Differentiation" were identified. The ID genes normally inhibit differentiation of cells, including neurons. The ID gene family showed abnormally high expression in the Mecp2 deficient mouse model and in Rett syndrome postmortem brain. These results suggest that increased expression of the ID genes may inhibit normal neuronal maturation, resulting in immature neurons and abnormal brain development in the Rett brain. These results could have relevance for future Rett treatments, as ID inhibitor drugs are currently being designed for potential cancer treatments.