A computational model predicts <i>Xenopus</i> meiotic spindle organization

Loughlin, Rose; Heald, Rebecca; Nédélec, François

doi:10.1083/jcb.201006076

Cited by 134 publications

(154 citation statements)

References 57 publications

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“…Here we performed simulations with Cytosim software (Nedelec and Foethke, 2007). This cytoskeleton simulator is based on a Langevin dynamics approach and offers the possibility to take into account numerous components in minimal computational time due to a semi-implicit numerical integration scheme (Kozlowski et al, 2007;Loughlin et al, 2010Loughlin et al, , 2011Ward et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

Centrosome Centering and Decentering by Microtubule Network Rearrangement

Letort¹,

Burute²

2017

Single Cell Biol

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The centrosome is positioned at the cell center by pushing and pulling forces transmitted by microtubules (MTs). Centrosome decentering is often considered to result from asymmetric, cortical pulling forces exerted in particular by molecular motors on MTs and controlled by external cues affecting the cell cortex locally. Here we used numerical simulations to investigate the possibility that it could equally result from the redistribution of pushing forces due to a reorientation of MTs. We first showed that MT gliding along cell edges and pivoting around the centrosome regulate MT rearrangement and thereby direct the spatial distribution of pushing forces, whereas the number, dynamics, and stiffness of MTs determine the magnitude of these forces. By modulating these parameters, we identified different regimes, involving both pushing and pulling forces, characterized by robust centrosome centering, robust off-centering, or "reactive" positioning. In the last-named conditions, weak asymmetric cues can induce a misbalance of pushing and pulling forces, resulting in an abrupt transition from a centered to an off-centered position. Taken together, these results point to the central role played by the configuration of the MTs on the distribution of pushing forces that position the centrosome. We suggest that asymmetric external cues should not be seen as direct driver of centrosome decentering and cell polarization but instead as inducers of an effective reorganization of the MT network, fostering centrosome motion to the cell periphery.

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Section: Resultsmentioning

confidence: 99%

Centrosome Centering and Decentering by Microtubule Network Rearrangement

Letort¹,

Burute²

2017

Single Cell Biol

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“…Nevertheless, approaches driven either in oocytes, eggs or extracts have generated an abundant literature, which has been attractive for modeling purposes. Computational models have been proposed to understand the self-organization of meiotic spindle (Loughlin et al, 2010;Schaffner and Jose, 2006;Schaffner and Jose, 2008). These models offer a coherent picture of how microtubule dynamic instability, flux, and nucleation contribute to self-organization of a structure in a steady state.…”

Section: Discussionmentioning

confidence: 99%

Comparing Pig and Amphibian Oocytes: Methodologies for Aneuploidy Detection and Complementary Lessons for MAPK Involvement in Meiotic Spindle Morphogenesis

Ješeta¹,

Bodart²

2012

Aneuploidy in Health and Disease

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“…Theoretical modeling has been instrumental for our understanding of how larger scale structures such as the spindle form (85,86). Recently, it was discovered that bipolar structures with antiparallel fluxing MTs as in a spindle could be formed in silico with dynamic MTs, an MT cross-linking force, and antiparallel sliding activity, and pole formation was achieved by the addition of a NuMA-like minus-end cross-linker and directed transport of MT depolymerization activity toward minus-ends (87). Realistic MT lifetimes and MT length distributions required dynamic instability and minus-end depolymerization activities, yet meiotic spindle assembly could only be modeled by simulating MT nucleation specifically throughout the spindle and not only from the chromatin zone.…”

Section: Assembly and Scaling Of Self-organized Microtubule Structuresmentioning

confidence: 99%

Building the Microtubule Cytoskeleton Piece by Piece

Alfaro-Aco

Petry

2015

Journal of Biological Chemistry

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The microtubule (MT) cytoskeleton gives cells their shape, organizes the cellular interior, and segregates chromosomes. These functions rely on the precise arrangement of MTs, which is achieved by the coordinated action of MT-associated proteins (MAPs). We highlight the first and most important examples of how different MAP activities are combined in vitro to create an ensemble function that exceeds the simple addition of their individual activities, and how the Xenopus laevis egg extract system has been utilized as a powerful intermediate between cellular and purified systems to uncover the design principles of selforganized MT networks in the cell. The microtubule (MT)2 cytoskeleton forms the skeletal framework that gives eukaryotic cells their shape and organizes their cytoplasm by positioning organelles, providing tracks for transport, and establishing cell polarity. In an interphase cell, the MT cytoskeleton is also critical for cell motility and a key constituent of cilia and flagella. During cell division, the MT cytoskeleton gets remodeled into a spindle structure that segregates chromosomes. Each of these functions relies on a specific MT architecture, which must be capable of rapid and prolonged change followed by an eventual resumption of a steady state to respond to the cellular environment and morphology changes during growth and differentiation.MTs are made of ␣/␤-tubulin heterodimers, which assemble into a polar, cylindrical structure in the presence of GTP and above the so-called critical concentration in vitro. MT growth phases alternate with swift shrinkage phases (dynamic instability), and their transitions are referred to as catastrophe (switching from growth to shrinkage) and rescue (switching from shrinkage to growth) (1). In cells, a plethora of different MT-associated proteins (MAPs) regulate the MT-inherent abilities of MT nucleation and dynamics ( Fig. 1A) (2). In addition, MT cross-linking proteins connect MTs into networks and molecular motors use MTs as tracks for cargo transport or transport MTs themselves (Fig. 1A). Altogether, different combinations of these four basic groups of MAP activities drive the self-organization of the MT cytoskeleton into discrete three-dimensional patterns (Fig. 1B) (3). Thus, they establish, maintain, and disassemble functional MT structures that are observed on the cellular level.Traditionally, individual MAPs were identified by loss-offunction experiments in cells followed by their detailed in vivo and in vitro characterization. During the past decade, highthroughput genomic and proteomic screens accelerated MAP discovery by cataloging RNAi phenotypes and identifying novel microtubule binders, resulting in comprehensive lists of candidates involved in organizing the MT cytoskeleton in various cell states (4 -7). Now, the challenge is to understand how these MAPs work together to establish the physiological MT architecture of the cell. What specific MAP building blocks can generate the MT networks that shape a dendrite or a polarized epithelial cell (...

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A computational model predicts Xenopus meiotic spindle organization

Abstract: Spatially dispersed nucleation and minus end–directed transport of microtubule end disassembly activity can lead to bipolar spindle assembly.

Cited by 134 publications

References 57 publications

Centrosome Centering and Decentering by Microtubule Network Rearrangement

Centrosome Centering and Decentering by Microtubule Network Rearrangement

Comparing Pig and Amphibian Oocytes: Methodologies for Aneuploidy Detection and Complementary Lessons for MAPK Involvement in Meiotic Spindle Morphogenesis

Building the Microtubule Cytoskeleton Piece by Piece

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