In development, reelin is secreted by Cajal-Retzius cells. Reelin acts as an extracellular ligand binding to ApoER2 and VLDLR on migrating neurons. A specific lysine residue on reelin binds to the first repeat on the ligand binding domain of ApoER2. This interaction with the two receptors activates intracellular processes that begin with the phosphorylation of Dab1, a tyrosine kinase phosphorylated protein which is encoded by the DAB1 gene. This protein associates with the NPXY motifs on the intracellular tails of ApoER2 and VLDLR. Upon reelin binding, Dab1 is phosphorylated by two tyrosine kinases, Fyn and Src. The phosphorylated Dab1 then causes further activation of these two kinases and others, including a phosphatidylinositol-3-kinase (PI3K). PI3K activation leads to inhibitory phosphorylation of the tau kinase glycogen synthase kinase 3 beta (GSK3B), which alters the activity of tau protein, a protein involved in stabilizing microtubules. This transduction is combined with the activation of other pathways that influence the cytoskeletal rearrangement necessary for proper cortical cell migration.