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Bagirathy Nadarajah

Publications and source records attributed to Bagirathy Nadarajah.

6 recordsLinked to original sources

Layering defect in p35 deficiency is linked to improper neuronal-glial interaction in radial migration.

Several genes essential for neocortical layering have been identified in recent years, but their precise roles in this process remain to be elucidated. Mice deficient in p35--an activator of cyclin-dependent kinase 5 (Cdk5)--are characterized by a neocortex that has inverted layering. To decipher the physiological mechanisms that underlie this defect, we compared time-lapse recordings between p35(-/-) and wild-type cortical slices. In the p35(-/-) neocortex, the classic modes of radial migration--somal translocation and locomotion--were largely replaced by a distinct mode of migration: branched migration. Branched migration is cell-autonomous, associated with impaired neuronal-glial interaction and rare in neurons of scrambler mice, which are deficient in Dab1. Hence, our findings suggest that inside-out layering requires distinct functions of Reelin and p35/Cdk5 signaling, with the latter being important for proper glia-guided migration.

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Radial glia and somal translocation of radial neurons in the developing cerebral cortex.

A series of recent studies have demonstrated that radial glia are neural precursors in the developing cerebral cortex. These studies have further implied that these cells are the sole precursor constituents of the dorsal forebrain ventricular zone that generate the projection neurons of the cortex. In view of these new findings, this review discusses radial neurons, a progeny of cortical neurons that are generated by radial glia and adopt somal translocation as the mode of migration.

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A novel method of labeling and characterizing migrating neurons in the developing central nervous system.

Neuronal migration, a discrete event in the developing nervous system, is currently being intensively investigated using a variety of anatomical and molecular approaches. Using 4-chloromethyl benzoyl amino tetramethyl rhodamine (CMTMR) coated particles, we describe here a novel and efficient method of tracer labeling to investigate cell migration in embryonic and postnatal brain. Further, we demonstrate that application of CMTMR facilitates the labeling of a large number of migrating cells and enables the characterization of their phenotypes with immunohistochemical and in situ hybridization techniques. We also illustrate that CMTMR labeling is ideally suited for time-lapse imaging of the behavior and dynamics of migrating cells.

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Ventricle-directed migration in the developing cerebral cortex.

It is believed that postmitotic neurons migrate away from their sites of origin in the germinal zones to populate distant targets. Contrary to this notion, we found, using time-lapse imaging of brain slices, populations of neurons positioned at various levels of the developing neocortex that migrate towards the cortical ventricular zone. After a pause in this proliferative zone, they migrate radially in the direction of the pial surface to take up positions in the cortical plate. Immunohistochemical analysis together with tracer labeling in brain slices showed that cells showing ventricle-directed migration in the developing cortex are GABAergic interneurons originating in the ganglionic eminence in the ventral telencephalon. We speculate that combinations of chemoattractant and chemorepellent molecules are involved in this ventricle-directed migration and that interneurons may seek the cortical ventricular zone to receive layer information.

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Modes of neuronal migration in the developing cerebral cortex.

The conventional scheme of cortical formation shows that postmitotic neurons migrate away from the germinal ventricular zone to their positions in the developing cortex, guided by the processes of radial glial cells. However, recent studies indicate that different neuronal types adopt distinct modes of migration in the developing cortex. Here, we review evidence for two modes of radial movement: somal translocation, which is adopted by the early-generated neurons; and glia-guided locomotion, which is used predominantly by pyramidal cells. Cortical interneurons, which originate in the ventral telencephalon, use a third mode of migration. They migrate tangentially into the cortex, then seek the ventricular zone before moving radially to take up their positions in the cortical anlage.

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