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

Gupta, Amitabh; Sanada, Kamon; Miyamoto, David T.; Rovelstad, Susan; Nadarajah, Bagirathy; Pearlman, Alan L.; Brunstrom, Janice E.; Tsai, Li‐Huei

doi:10.1038/nn1151

Cited by 104 publications

(82 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar branched phenotype was reported in migrating neurons in the cortex of the p35 mutant 66 , where it was thought to contribute to altered cortical lamination. Since p35/CDK5 complex interacts with DCX, it is possible that this interaction relates to the branched phenotype 67 .…”

Section: Plays An Essential Role In Maintaining Bipolar Morphologysupporting

confidence: 70%

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

Section: Plays An Essential Role In Maintaining Bipolar Morphologysupporting

confidence: 70%

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

et al. 2006

View full text Add to dashboard Cite

show abstract

“…p35 is the most important regulatory subunit of Cdk5 during neurodevelopment, [38][39][40] and we confirmed that it interacts with Cdk5 during cell death. 28 Cleavage of p35 to p25 by calpain has been linked to activation of Cdk5.…”

Section: Introductionsupporting

confidence: 75%

p53, Apaf-1, caspase-3, and -9 are dispensable for Cdk5 activation during cell death

Lin

Zakeri

2005

Cell Death Differ

View full text Add to dashboard Cite

Cyclin-dependent kinase 5 (Cdk5) is a member of the cyclindependent kinase family that is mostly seen in neurons, does not vary with cell cycle, and is activated in many neurodegenerative disorders and other non-neuronal pathologies, but its relationship to non-neuronal apoptosis is not understood, nor is the control of the activation of Cdk5 by its activators. The most widely studied activator of Cdk5, p35, is cleaved to p25 by calpain, an event that has been linked with activation of Cdk5 and neuronal death. Here we report that calpain-mediated Cdk5/p25 activation accompanies nonneuronal as well as neuronal cell death, suggesting that the p35/calpain/p25/Cdk5 activation sequence is a general feature of cell death. We further demonstrate that Cdk5 can be activated in the absence of p53, Apaf-1, caspase-9, and -3 during cell death, indicating that its activation relates more to cell death than to a specific pathway of apoptosis.

show abstract

“…In contrast, radially migrating neurons seem to have a single leading process (Rakic 1972). Interestingly, defects in the interaction between pyramidal cells and radial glial fibers frequently lead to aberrant branching of the leading process (Elias et al 2007;Gupta et al 2003), which suggest that the bipolar morphology of radially migrating neurons might be imposed by glialguided locomotion.…”

Section: Leading Process Dynamicsmentioning

confidence: 99%

“…Ndel1 is required for targeting Lis1 and dynein to the centrosome, and facilitates the nucleation and anchoring of microtubules to the centrosome (Guo et al 2006). In addition, Ndel1 facilitates the interaction between Lis1 and dynein and regulates dynein-mediated retrograde transport (Gupta et al 2003;Li et al 2005;Mesngon et al 2006;Smith et al 2000). Disruption of Lis1 function abolishes centrosomenucleus coupling, increasing the distance between the two organelles.…”

Section: Nucleokinesismentioning

confidence: 99%

Guiding Neuronal Cell Migrations

Marı́n¹,

Valiente²,

Ge³

et al. 2010

Cold Spring Harbor Perspectives in Biology

359

345

View full text Add to dashboard Cite

Neuronal migration is, along with axon guidance, one of the fundamental mechanisms underlying the wiring of the brain. As other organs, the nervous system has acquired the ability to grow both in size and complexity by using migration as a strategy to position cell types from different origins into specific coordinates, allowing for the generation of brain circuitries. Guidance of migrating neurons shares many features with axon guidance, from the use of substrates to the specific cues regulating chemotaxis. There are, however, important differences in the cell biology of these two processes. The most evident case is nucleokinesis, which is an essential component of migration that needs to be integrated within the guidance of the cell. Perhaps more surprisingly, the cellular mechanisms underlying the response of the leading process of migrating cells to guidance cues might be different to those involved in growth cone steering, at least for some neuronal populations.

show abstract

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

Cited by 104 publications

References 50 publications

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

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

p53, Apaf-1, caspase-3, and -9 are dispensable for Cdk5 activation during cell death

Guiding Neuronal Cell Migrations

Contact Info

Product

Resources

About