Doublecortin Is a Developmentally Regulated, Microtubule-Associated Protein Expressed in Migrating and Differentiating Neurons

Francis, Fiona; Koulakoff, Annette; Boucher, Dominique; Chafey, Philippe; Schaar, Bruce T.; Vinet, M.; Friocourt, Gaëlle; McDonnell, Nathalie; Reiner, Orly; Kahn, Axel; McConnell, Susan K.; Berwald‐Netter, Yoheved; Denoulet, Philippe; Chelly, Jamel

doi:10.1016/s0896-6273(00)80777-1

Cited by 925 publications

(744 citation statements)

References 46 publications

Supporting

Mentioning

697

Contrasting

Unclassified

Order By: Relevance

“…We evaluated this function using co-cultures of astrocytes derived from cortices of mice bearing an actin-green fluorescent protein (GFP) transgene, and cortical neurons derived from 16-day-old wild-type mouse embryos. Embryonic brain cellular suspension was added upon actin-GFP astrocytes seeded at low density and treated for 7 days with TGFa, and the migration of immature neurons (doublecortin positive (Francis et al, 1999); Figure 4b) along the glial bipolar processes was monitored 24 h later using time-lapse microphotography as described (Gregg and Weiss, 2003). The bipolar processes extended by TGFa-treated astrocytes supported neuronal migration (Figure 4e-i).…”

Section: Tgfa Dedifferentiates Astrocytesmentioning

confidence: 99%

See 1 more Smart Citation

Transforming growth factor α promotes sequential conversion of mature astrocytes into neural progenitors and stem cells

et al. 2006

View full text Add to dashboard Cite

Section: Tgfa Dedifferentiates Astrocytesmentioning

confidence: 99%

“…Neurons were prepared from cortices of C57Bl6 embryos at E16 following previously described procedures (Francis et al, 1999). They were seeded onto the astrocyte monolayer at a density of 260 000 cells/cm 2 and further maintained for up to 4 days in defined medium containing or not containing TGFa.…”

Section: Neuronal Migration Assaymentioning

confidence: 99%

Transforming growth factor α promotes sequential conversion of mature astrocytes into neural progenitors and stem cells

et al. 2006

View full text Add to dashboard Cite

“…Translocation of the nucleus towards the position of the centrosome 42 . As DCX localizes to the microtubules of the perinuclear cage, the leading process and the growth cones [43][44][45] , we examined for defects in each of these. We first tested for a defect in the latter two events.…”

Section: Decreased Migration Of Neurons Exiting Svza But No Apparent mentioning

confidence: 99%

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

et al. 2006

View full text Add to dashboard Cite

The ability of the mature mammalian nervous system to continually produce neuronal precursors is of considerable importance, as manipulation of this process might one day permit the replacement of cells lost as a result of injury or disease. In mammals, the anterior subventricular zone (SVZa) region is one of the primary sites of adult neurogenesis. Here we show that Doublecortin (DCX), a widely used marker for newly generated neurons, when deleted in mouse results in a severe morphological defect in the rostral migratory stream and delayed neuronal migration that is independent of direction or responsiveness to Slit chemorepulsion. DCX is required for nuclear translocation and maintenance of bipolar morphology during migration of these cells. Our data identifies a critical function for DCX in the movement of newly generated neurons in the adult brain.In the rodent and primate brain, the anterior region of the lateral ventricle and the hippocampus are the primary sites of adult neurogenesis [1][2][3][4][5][6][7] . These neuroblasts, upon completing migration, are capable of maturing into fully differentiated neurons, integrating into local synaptic circuits and may be important in adult cognitive processing [8][9][10][11] .The mechanisms controlling the targeted translocation of large numbers of cells to the olfactory bulb (OB) over a considerable distance (>5 mm in the adult mouse) are an issue of intense investigation. These neurons translocate using a process known as chain migration, whereby the cells use each other as the migratory substrate 12 . These newly generated neurons are derived from SVZa glial fibrillary acidic protein (GFAP)-positive astrocytes 13,14 , which also ensheath them as they move through extensive interconnected networks along the lining of the lateral ventricle in the rostral forebrain and the rostral migratory stream (RMS) 15 . There, they are under the control of extracellular migration guidance cues, including the secreted ligands Slit and Reelin [16][17][18][19] , the receptors ErbB4 and Deleted in Colorectal Carcinoma (DCC) 20,21 , as well as integrins and neural cell adhesion molecule [21][22][23] . Upon reaching the bulb, the neurons turn and migrate in a radial direction 24 , integrating into either the granule cell layer or the periglomerular network 25 . 3The X-linked gene doublecortin (DCX) is mutated in some patients with the severe neuronal migration defect called classical lissencephaly or double cortex syndrome 26,27 . This migration defect is likely to be cell autonomous, because in females with a heterozygous mutation, approximately half of the neurons are misplaced within the cerebral cortex as would be expected from random X-chromosome inactivation. As a result, males display a four-layered agyric cortex and females display a subcortical band of heterotopic neurons. It was surprising, therefore, that the Dcx knockout mice displayed no appreciable defect in cortical neuronal lamination or positioning 28 . One possible explanation for these species differences ...

show abstract

“…Proliferating cells were immunocytochemically stained for endogenous Ki67 nucleoprotein, which is expressed during the cell cycle [25]. To show newly generated cells of neuronal lineage, we used an antibody against Doublecortin (DCX), a microtubule-associated protein expressed during the migration of neurons and the growth of their neurites [26][27][28]. Pyknotic cells were used as indicators of neuronal death [29,30].…”

Section: Introductionmentioning

confidence: 99%

A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice

Klaus

Hauser

Slomianka

et al. 2009

Behavioural Brain Research

View full text Add to dashboard Cite

A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice Klaus, F; Hauser, T; Slomianka, L; Amrein, I; Lipp, H P Klaus, F; Hauser, T; Slomianka, L; Amrein, I; Lipp, H P (2009). A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice. A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice Abstract Exercise is one of the best-known stimulators of adult hippocampal neurogenesis, but it is not known if voluntary changes in the intensity of exercise are accompanied by changes in neurogenesis. In this study we investigated whether a reward influences the performance in a running wheel and the rate of cell proliferation, neuronal differentiation and cell death in C57BL/6 mice. Mice had free access to a running wheel during the first week of the experiment. In the second week, animals were rewarded for their performance and compared to normal voluntary running and control mice. A reward significantly increased the performance by 78% when compared to the non-rewarded performance of the first week.The performance of the non-rewarded runners remained relatively constant. Fourteen days of exercise significantly increased cell proliferation by 27% and the number of doublecortin immunoreactive cells by 46%. A reward and the associated increase of performance did not modulate proliferation, cell death or the number of cells entering the neuronal lineage. We suggest that, in C57BL/6 mice, either exercise increases adult hippocampal neurogenesis to a ceiling value, which is reached by a performance at or below the level achieved by voluntary wheel running, or that a possible positive effect of increased running-wheel activity is balanced by stress resulting from rewarded running, which is no longer performed on a strictly voluntary basis. We suggest that, in C57BL/6 mice, either exercise increases adult hippocampal neurogenesis to a ceiling value, which is reached by a performance at or below the level achieved by voluntary wheel running, or that a possible positive effect of increased is balanced by stress resulting from rewarded running, which is no longer performed on a strictly voluntary basis.

show abstract

Doublecortin Is a Developmentally Regulated, Microtubule-Associated Protein Expressed in Migrating and Differentiating Neurons

Cited by 925 publications

References 46 publications

Transforming growth factor α promotes sequential conversion of mature astrocytes into neural progenitors and stem cells

Transforming growth factor α promotes sequential conversion of mature astrocytes into neural progenitors and stem cells

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

A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice

Contact Info

Product

Resources

About