Reelin Gene Expression and Regulation in Normal Brain Development

Researchers at the Center for Childhood Cancer Research, including Tom Curran, PhD, FRS, are studying processes of normal brain development to find possible drug targets for several pediatric brain tumors.

Studying brain cell signaling pathways can lead to a better understanding of normal brain development. It may also help researchers identify genes and proteins (when dysregulated) that result in brain tumor formation.  One area of focus is the role of the reelin (Reln) gene and its protein product in normal brain development.

The reelin (Reln) gene product is a large, extracellular protein that is secreted by several early neuron populations in the developing brain. Previous studies with genetically engineered transgenic mice and conditional mutant mouse cell lines revealed that reelin plays a critical role in neuronal cell migration and positioning in brain development. 

Reelin is part of a cell signaling pathway that is thought to exert its action by inducing phosphorlyation of Disabled-1 (Dab1) through the Src family tyrosine kinases Fyn and Src.

Molecular and cellular studies using mutant transgenic mice and conditional mouse mutant cell lines generated at CHOP are underway to determine the molecular events downstream of the Reln gene that mediate its function in normal brain development.

This has led to the identification of other proteins that likely play an important role in the reelin pathway to control brain development.

Ultimately, by understanding processes that govern normal brain development we hope to determine new approaches and treatments for rare but very devastating pediatric brain tumors.