Doublecortin Is a Microtubule-Associated Protein and Is Expressed Widely by Migrating Neurons

Abstract

Doublecortin (DCX) is required for normal migration of neurons into the cerebral cortex, since mutations in the human gene cause a disruption of cortical 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 during embryonic and postnatal development. DCX protein localization overlaps with microtubules in cultured primary cortical neurons, and this overlapping expression is disrupted by microtubule depolymerization. DCX coassembles with brain microtubules, and recombinant DCX stimulates the polymerization of purified tubulin. Finally, overexpression of DCX in heterologous cells leads to a dramatic microtubule phenotype that is resistant to depolymerization. Therefore, DCX likely directs neuronal migration by regulating the organization and stability of microtubules.

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

“…We now show that deletion of Dcx leads to a defect in nuclear translocation that was not evident by measurement of N-C coupling alone. As DCX is a potent microtubule-associated protein and localized prominently to perinuclear microtubules 31,43 , we hypothesize that it is required for formation or stabilization of these microtubules, or in mediating transport of the nucleus along these microtubules, possibly in association with the LIS1/Ndel1/dynein complex.…”

“…DCX has become a widely used marker for newly generated neuroblasts in proliferative zones in adult 14,31,53,54 . In these regions, DCX is expressed exclusive of GFAP positive cells, and appears to be one of the earliest markers for cells transitioning from astrocytic glia to neuroblasts in the SVZ and RMS 32 .…”

Manipulation of Neural Precursors in situ Induction of Neurogenesis in the Neocortex of Adult Mice

“…No BrdUϩ/ Dcxϩ cells were found in the corpus callosum or cortex of control animals. However, they exist in the rostral migratory stream of both controls and experimentals, as previously described (Gleeson et al 1999;Francis et al 1999). Newly born BrdUϩ/Dcxϩ neurons within the corpus callosum displayed morphologies characteristic of migrating neurons, while newborn Dcxϩ neurons located in deep layers of cortex displayed more complex morphologies with apical processes that suggest their further differentiation.…”

“…25 , NO . 6 First, subsets of BrdU ϩ precursors expressed Doublecortin, a protein expressed exclusively in immature, typically migrating neurons (Gleeson et al 1999;Francis et al 1999), and Hu, an early neuronal marker (Marusich et al 1994;Barami et al 1995). We observed no new neurons in control, intact cortex.…”

“…In experimental mice only, newborn BrdUϩ/Dcxϩ neurons with migratory morphologies appeared to migrate from the SVZ through the corpus callosum (Figure 4, Panels a-d) and into experimental regions of cortex (Figure 4, Panels e,f). Doublecortin is a microtubule-associated protein that is exclusively expressed in immature migrating and differentiating neurons, but is not detectable in mature neurons (Gleeson et al 1999;Francis et al 1999). Confocal analysis confirmed that these BrdUϩ cells express Doublecortin ( Figure 4, Panels c,d).…”