Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons

Doublecortin (DCX) is required for normal migration of neurons into the cer ebral cortex, since mutations in the human gene cause a disruption of corti cal neuronal migration. To date, little is known about the distribution of DCX protein or its function. Here, we demonstrate that DCX is expressed in migrating neurons throughout the central and peripheral nervous system duri ng embryonic and postnatal development. DCX protein localization overlaps w ith microtubules in cultured primary cortical neurons, and this overlapping expression is disrupted by microtubule depolymerization. DCX coassembles w ith brain microtubules, and recombinant DCX stimulates the polymerization o f purified tubulin. Finally, overexpression of DCX in heterologous cells le ads to a dramatic microtubule phenotype that is resistant to depolymerizati on. Therefore, DCX likely directs neuronal migration by regulating the orga nization and stability of microtubules.