The centrosome in neuronal development

Higginbotham, Holden; Gleeson, Joseph G.

doi:10.1016/j.tins.2007.04.001

Cited by 208 publications

(175 citation statements)

References 57 publications

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“…Similar defects are observed in neurons with Ndel1 or dynein loss of function (Aumais et al 2001;Dawe et al 2001;Sasaki et al 2000;Shu et al 2004;, suggesting that Lis1, Ndel1, and dynein regulate the microtubule network that couples the centrosome to the nucleus. Perturbation of this complex may contribute to the cortical lamination defects observed in lissencephaly patients (Ayala et al 2007;Higginbotham and Gleeson 2007;Tsai and Gleeson 2005).…”

Section: Nucleokinesismentioning

confidence: 99%

Guiding Neuronal Cell Migrations

Marı́n¹,

Valiente²,

Ge³

et al. 2010

Cold Spring Harbor Perspectives in Biology

372

351

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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.

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Section: Nucleokinesismentioning

confidence: 99%

Guiding Neuronal Cell Migrations

Marı́n¹,

Valiente²,

Ge³

et al. 2010

Cold Spring Harbor Perspectives in Biology

372

351

View full text Add to dashboard Cite

show abstract

“…Previous studies have indicated that microtubules radiating from the centrosome are anchored to the leading process and nucleus. The centrosome is thought to relay the force generated by leading process extension to the nucleus via the microtubule bundles (13,20). We thus analyzed the microtubule cytoskeleton in migrating granule cells in a reaggregate culture of external granule layer cells (16).…”

Section: Large-amplitude Saltatory Movements Of the Nucleus In Radiallymentioning

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

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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

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“…Soma translocation toward the leading process is achieved in two consecutive steps. First the centrosome together with the Golgi apparatus moves forward, leading to the formation of a swelling ahead of the nucleus (Bellion et al, 2005;Schaar and McConnell, 2005;Higginbotham and Gleeson, 2007). Second, the nucleus moves toward the swelling in a step known as nucleokinesis.…”

Section: Introductionmentioning

confidence: 99%

Actomyosin Contraction at the Cell Rear Drives Nuclear Translocation in Migrating Cortical Interneurons

Martini

Valdeolmillos²

2010

Journal of Neuroscience

111

134

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Neuronal migration is a complex process requiring the coordinated interaction of cytoskeletal components and regulated by calcium signaling among other factors. Migratory neurons are polarized cells in which the largest intracellular organelle, the nucleus, has to move repeatedly. Current views support a central role for pulling forces that drive nuclear movement. The participation of actomyosin driven forces acting at the nucleus rear has been suggested, however its precise contribution has not been directly addressed. By analyzing interneurons migrating in cortical slices of mouse brains, we have found that nucleokinesis is associated with a precise pattern of actin dynamics characterized by the initial formation of a cup-like actin structure at the rear nuclear pole. Time-lapse experiments show that progressive actomyosin contraction drives the nucleus forward. Nucleokinesis concludes with the complete contraction of the cup-like structure, resulting in an actin spot at the base of the retracting trailing process. Our results demonstrate that this actin remodeling requires a threshold calcium level provided by low-frequency spontaneous fast intracellular calcium transients. Microtubule stabilization with taxol treatment prevents actin remodeling and nucleokinesis, whereas cells with a collapsed microtubule cytoskeleton induced by nocodazole treatment, display nearly normal actin dynamics and nucleokinesis. In summary, the results presented here demonstrate that actomyosin forces acting at the rear side of the nucleus drives nucleokinesis in tangentially migrating interneurons in a process that requires calcium and a dynamic cytoskeleton of microtubules.

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The centrosome in neuronal development

Cited by 208 publications

References 57 publications

Guiding Neuronal Cell Migrations

Guiding Neuronal Cell Migrations

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

Actomyosin Contraction at the Cell Rear Drives Nuclear Translocation in Migrating Cortical Interneurons

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