Reelin-induced tyrosine [corrected] phosphorylation of disabled 1 during neuronal positioning.

The reelin (reln) and disabled 1 (dab1) genes both ensure correct neuronal positioning during brain development. We have found that the intracellular Dab1 protein receives a tyrosine phosphorylation signal from extracellular Reln protein. Genetic analysis shows that reln function depends on dab1, and vice versa, as expected if both genes are in the same pathway. Dab1 is expressed at a higher level, yet phosphorylated at a lower level, in reln mutant embryo brains. In primary neuronal cultures, Dab1 tyrosine phosphorylation is stimulated by exogenous Reln. These results suggest that Reln regulates neuronal positioning by stimulating Dab1 tyrosine phosphorylation.