Disease relevance of Dcx

• A basic helix-loop-helix transcription factor NeuroD at 7 and 14 days and an immature migrating neuronal marker doublecortin at 14 days after ischemia were expressed transiently in proliferative cells [1].
• We addressed this issue by quantifying the number of cells that are positive for doublecortin (DCX, a marker of new neurons) in the DG of adult F344 rats at 16 days and 5 months after an intracerebroventricular kainic acid (ICV KA) administration or after graded intraperitoneal KA (IP KA) injections, models of temporal lobe epilepsy (TLE) [2].
• In the inner part, the somata of cells in the ganglion cell layer, in the distal row of the neuroblastic layer and profiles in the inner plexiform layer showed doublecortin immunoreactivity up to postnatal day 1 (P1) [3].

High impact information on Dcx

• RNAi reveals doublecortin is required for radial migration in rat neocortex [4].
• We present evidence that Dcx/microtubule interactions are negatively controlled by Protein Kinase A (PKA) and the MARK/PAR-1 family of protein kinases [5].
• Cells labeled with BrdUrd coexpressed the immature neuronal markers doublecortin and proliferating cell nuclear antigen but did not express the more mature cell markers NeuN and Hu, suggesting that they were nascent neurons [6].
• Morphological findings (doublecortin staining) suggest permanent progenitor cell loss in some areas of SGZ [7].
• Doublecortin kinase-2, a novel doublecortin-related protein kinase associated with terminal segments of axons and dendrites [8].

Biological context of Dcx

• In utero RNA interference (RNAi) of Dcx in rats, in contrast, creates an animal model of SBH [9].
• Functional studies have revealed microtubule binding and polymerization activities of the doublecortin domain, yet little is known regarding the enzymatic properties and regulation of the kinase catalytic domain [10].
• During development of the central nervous system, expression of the microtubule binding protein doublecortin (DCX) is associated with migration of neuroblasts [11].
• The effects of HI injury on SVZ cell proliferation and neurogenesis were examined 1-3 wk later by morphometric measurement of dorsolateral SVZ size; by immunoassays to detect incorporation of bromodeoxyuridine (BrdU) in proliferating cells; and by immunoassays of doublecortin, a microtubule-associated protein expressed only by immature neurons [12].
• To address the issues of direct versus indirect control and regional specificity we investigated the colocalization of immunoreactivity for a proliferating cell marker, Ki-67, and a marker for migrating and differentiating cells with a neuronal phenotype, doublecortin, with the expressions of mRNA for estrogen receptors alpha and beta [13].

Anatomical context of Dcx

• A subpopulation of RPE- and CB-derived progenitor cells expressed the neurogenesis-specific protein doublecortin (DCX) [14].
• Adult retinal pigment epithelium cells express neural progenitor properties and the neuronal precursor protein doublecortin [14].
• Efficacy of doublecortin as a marker to analyse the absolute number and dendritic growth of newly generated neurons in the adult dentate gyrus [15].
• Doublecortin (DCX) is a protein required for normal neuronal migration in the developing cerebral cortex, where it is widely expressed in both radially and tangentially migrating neuroblasts [16].
• Doublecortin is 40 kDa microtubule-associated phosphoprotein required for neuronal migration and differentiation in various regions of the developing central nervous system [3].

Associations of Dcx with chemical compounds

• Tissue sections were double-stained for BrdU and the cell-type markers NG2, OX-42, RIP, S-100beta, Doublecortin, or NeuN [17].
• Infusion of an antimitotic agent (cytosine-beta-D-arabiofuranoside, Ara-C) onto the ipsilateral cortex eliminated more than 98% of actively proliferating cells in the SVZ and doublecortin-positive cells in the ipsilateral striatum [18].
• Some of them were found to colocalize with the neuronal markers doublecortin, HuC/D, or neuronal-specific antigen (NeuN), demonstrating that neurogenesis does occur within the DVC of adult rat [19].
• Using immunohistochemistry we have studied the expression of PSA-NCAM and doublecortin (DCX; another protein implicated in neuronal structural plasticity) in the piriform cortex of adult rats subjected either to 21 days of chronic restraint stress or to oral corticosterone administration during the same period [20].
• Following induction of lesions by striatal injection of 6-OHDA or QA, the number of cells positive for doublecortin (DCX) was strongly increased in the striatum; however, there was no change in the number of DCX-positive cells following 6-OHDA injection into the SN [21].

Co-localisations of Dcx

• In the adult rostral migratory stream, doublecortin colocalizes in migrating neurons with a phospho-FIGQY bearing L1 CAM different from neurofascin [22].

Regulatory relationships of Dcx

• Reducing the expression of stathmin or doublecortin with an antisense oligonucleotide inhibited the migration of new neurons from the subventricular zone to the olfactory bulb via the rostral migratory stream [23].

Other interactions of Dcx

• Dividing Pax6- and Olig2-positive neural progenitor cells continually gave rise to doublecortin-positive new neurons in this region [24].
• Single labeling immunocytochemistry for newly born neurons using doublecortin, as well as double labeling using an additional antibody to glial fibrillary acidic protein (GFAP) to label astrocytes were used at the light microscopic level [25].
• Stathmin immunohistochemistry in adult rodent brain revealed prominent expression in neuroproliferative zones and neuronal migration pathways, a pattern that resembles the expression of doublecortin, which is implicated in neuronal migration [23].
• We now show that, although the rostral migration of the newly born SVZ cells and their differentiation into neurons in the olfactory bulb were not affected by the lesion, numerous cells expressing the neuroblast marker doublecortin migrated laterally in the striatum and corpus callosum 5 days postinjury [26].
• A new activity of doublecortin in recognition of the phospho-FIGQY tyrosine in the cytoplasmic domain of neurofascin [22].

Analytical, diagnostic and therapeutic context of Dcx

• At 2, 4, and 10 weeks after ischemia, immunocytochemistry was performed with immature neuronal (doublecortin), mature neuronal (neuronal nuclei antigen) and glial (calcium-binding protein beta S100beta) markers [27].
• We have investigated the expression and cellular localization of doublecortin in the developing rat retina using immunocytochemistry and Western blot analysis [3].
• Furthermore, doublecortin immunoelectron microscopy was used to examine the ultrastructural relationship between newborn neurons and astrocytes in the adult dentate gyrus [25].

References