Cytology and neuron-glial apposition of migrating cerebellar granule cells in vitro

Gregory, William A.; Edmondson, James C.; Hatten, Mary E.; Mason, Carol A.

doi:10.1523/jneurosci.08-05-01728.1988

Cited by 191 publications

(145 citation statements)

References 24 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…In contrast, our imaging studies revealed nuclear migration past the centrosome, excluding the pulling effect of the centrosome as its major driving force. Our results are supported by previous electron microscopic observations that centrosomes are located to the side of cell bodies in migrating neurons (9,10). Studies using dissociated granule cells have indicated that small-amplitude movements of the soma (1.3 m on average) were preceded by centrosomal movements every 3-5 min (7).…”

Section: Discussionsupporting

confidence: 91%

“…Instead, the centrosome is considered to play a key role in driving nuclear migration in neurons. The centrosome typically precedes and is coupled to the nucleus via perinuclear microtubules that envelop and capture the nucleus (6)(7)(8)(9)(10)(11). Current models suggest that the centrosome first moves into the leading process and serves as a cue for forward displacement of the nucleus along the microtubules (7,8,(12)(13)(14).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Microtubule-based nuclear movement occurs independently of centrosome positioning in migrating neurons

Umeshima

Hirano²,

Kengaku³

2007

Proc. Natl. Acad. Sci. U.S.A.

171

147

View full text Add to dashboard Cite

During neuronal migration in the developing brain, it is thought that the centrosome precedes the nucleus and provides a cue for nuclear migration along the microtubules. In time-lapse imaging studies of radially migrating granule cells in mouse cerebellar slices, we observed that the movements of the nucleus and centrosome appeared to occur independently of each other. The nucleus often migrated ahead of the centrosome during its saltatory movement, negating the supposed role of the centrosome in pulling the nucleus. The nucleus was associated with dynamic microtubules enveloping the entire nucleus and stable microtubules extending from the leading process to the anterior part of the nucleus. Neither of these perinuclear microtubules converged at the centrosome. Disruption or excess formation of stable microtubules attenuated nuclear migration, indicating that the configuration of stable microtubules is crucial for nuclear migration. The inhibition of LIS1 function, a regulator of a microtubule motor dynein, specifically blocks nuclear migration without affecting the coupling of the centrosome and microtubules in the leading process, suggesting that movements of the nucleus and centrosome are differentially regulated by dynein motor function. Thus, the nucleus moves along the microtubules independently of the position of the centrosome in migrating neurons.neuronal migration ͉ nucleus ͉ LIS1 ͉ acetylated tubulin ͉ tyrosinated tubulin

show abstract

Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Microtubule-based nuclear movement occurs independently of centrosome positioning in migrating neurons

Umeshima

Hirano²,

Kengaku³

2007

Proc. Natl. Acad. Sci. U.S.A.

171

147

View full text Add to dashboard Cite

show abstract

“…During neuronal migration, the centrosome of the cell is uniformly positioned in front of the nucleus [63][64][65] , leading to a model in which the nucleus is translocated along microtubules in the "minus" direction through "minus"-end directed motors including dynein. Indeed, disruption of dynein function, or alterations in LIS1 or Ndel1, which are dynein components, similarly lead to alterations in this coupling, as measured by an increased distance between the nucleus and centrosome (i.e.…”

Section: Plays An Essential Role In Translocation Of the Nucleusmentioning

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

“…During migration, the Golgi, centrosome, and associated microtubule networks polarize the neuron in the direction of movement ( Fig. 3; Edmondson and Hatten 1987;Gregory et al 1988;Hatten 1999). Whereas the extending growth cone forms focal adhesions at the leading edge, migrating cells establish a broad interstitial junction beneath the cell soma (Gregory et al 1988).…”

Section: Polarity Proteins In Glial-guided Cns Migrationmentioning

confidence: 99%

Neuronal polarity in CNS development

Solecki¹,

Govek²,

Tomoda³

et al. 2006

Genes Dev.

View full text Add to dashboard Cite

The diversity of neuronal morphologies and the complexity of synaptic connections in the mammalian brain provide striking examples of cell polarity. Over the past decade, the identification of the PAR (for partitioningdefective) proteins, their function in polarity in the Caenorhabditis elegans zygote, and the conservation of polarity proteins related to the PAR polarity complex in Drosophila and vertebrates, kindled intense interest in polarity pathways. Although the existence of a conserved polarity protein complex does not prove that these proteins function the same way in different systems, the emergence of an evolutionarily conserved mechanism that regulates cell polarity provides an exciting opportunity to define the role of polarity proteins in the generation of the diverse array of cell types and patterns of connections in the developing mammalian brain. This review addresses emerging genetic, molecular genetic, biochemical, and cell biological approaches and mechanisms that control neuronal polarity, focusing on recent studies using the neonatal cerebellum and hippocampus as model systems.The Caenorhabditis elegans embryo is a model system for studying cell polarity. Three PAR (for partitioningdefective) polarity proteins localize in the anterior cortex of the one-cell embryo: PAR-3, which contains three PDZ domains; PAR-6, which contains a single PDZ domain and a G-protein-binding, CRIB-like domain; and PKC-3, an atypical protein kinase C (abbreviated as aPKC, PKC). In Drosophila, homologs of the C. elegans PAR proteins are essential for the emergence of cellularity, and for asymmetric division of neuroblasts ( Many features of intercellular junctions are conserved across species from yeast to vertebrates. The apical junction in yeast shares common features with the Drosophila zonula adherens (ZA) junction and ZA junctions of mammalian epithelia, including a band of actin, the transmembrane adhesion proteins, and associated cytoplasmic proteins such as ␤-catenin. Polarity proteins that establish the polarity of intercellular junctions of Drosophila epithelia are related to vertebrate polarity proteins that generate intercellular junctions in increasingly complex, multilayered vertebrate epithelia (Fig. 1). In mammalian epithelia, the first step in epithelial cell polarization is the formation of adhesion junctions between cells. Two classes of transmembrane adhesion proteins, cadherins and nectins, initiate adhesions between epithelial cells. Aggregation of adhesion sites leads to the recruitment of cytoskeletal proteins; the association of the intracellular domains of cadherins and nectin activates the Cdc42 and Rac GTPase pathways. After the adherens junction forms, a second adhesion site forms at the apical side of the cell, which becomes a tight junction. In polarized mammalian epithelial cells, the conserved polarity proteins PAR-3/ASIP, PAR-6, and aPKC localize to the tight junction. Recent studies suggest that Par3 and Par6/aPKC form complexes with other polarity proteins as well (Gao and Macara...

show abstract

Cytology and neuron-glial apposition of migrating cerebellar granule cells in vitro

Cited by 191 publications

References 24 publications

Microtubule-based nuclear movement occurs independently of centrosome positioning in migrating neurons

Microtubule-based nuclear movement occurs independently of centrosome positioning in migrating neurons

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

Neuronal polarity in CNS development

Contact Info

Product

Resources

About