Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces

Howard, Jonathon; Garzón-Coral, Carlos

doi:10.1002/bies.201700122

Cited by 44 publications

(52 citation statements)

References 106 publications

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“…In support of pushing, a more recent reevaluation of large asters has indicated that they also contain branched microtubules (Ishihara et al, 2014), thus suggesting that a pushing-based mechanisms could potentially operate. Moreover, it has been argued that even in large cells (circa 50µm) microtubule pushing forces can center centrosomes, and indeed that the pushing force per individual polymerizing microtubule (5-10pN) is equivalent to dyneinbased (1-7pN) pulling forces (Howard and Garzon-Coral, 2017). Thus, in Leech zygotes the cytoplasmic pulling-based mechanism for mitotic spindle centering may not operate, since the whole mitotic apparatus moves in the direction of the shortest microtubules, i.e.…”

Section: Ucd In Zygotes Of Spiralians (Cortical Contraction or Asymmementioning

confidence: 99%

Emergence of Embryo Shape During Cleavage Divisions

McDougall¹,

Chênevert²,

Godard³

et al. 2019

Results and Problems in Cell Differentiation

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Cells are arranged into species-specific patterns during early embryogenesis. Such cell division patterns are important since they often reflect the distribution of localized cortical factors from eggs/fertilized eggs to specific cells as well as the emergence of organismal form. However, it has proven difficult to reveal the mechanisms that underlie the emergence of cell positioning patterns that underlie embryonic shape, likely because a system-level approach is required that integrates cell biological, genetic, developmental and mechanical parameters. The choice of organism to address such questions is also important. Because ascidians display the most extreme form of invariant cleavage pattern amongst the metazoans, we have been analyzing the cell biological mechanisms that underpin three aspects of cell division (unequal cell division (UCD), oriented cell division (OCD), and asynchronous cell cycles) which affect the overall shape of the blastula-stage ascidian embryo composed of 64 cells. In ascidians, UCD creates two small cells at the 16-cell stage that in turn undergo two further successive rounds of UCD. Starting at the 16-cell stage, the cell cycle becomes asynchronous whereby the vegetal half divides before the animal half, thus creating 24, 32, 44 then 64-cell stages. Perturbing either UCD or the alternate cell division rhythm perturbs cell position. By analyzing cell shape, we discovered that cell shape propagates, via cell-cell contact, throughout the embryo following UCD and alternate/asynchronous cell division to create the ascidianspecific invariant cleavage pattern via OCD in the longest length of the apical surface of blastomeres.

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Section: Ucd In Zygotes Of Spiralians (Cortical Contraction or Asymmementioning

confidence: 99%

Emergence of Embryo Shape During Cleavage Divisions

McDougall¹,

Chênevert²,

Godard³

et al. 2019

Results and Problems in Cell Differentiation

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“…Cortical dynein generates pulling forces along these astral microtubules to promote spindle motion (reviewed by Kotak and Gönczy, 2013;McNally, 2013). Pushing forces of astral microtubules against the cortex have also been recently proposed to be involved in spindle positioning in Caenorhabditis elegans embryos (Howard and Garzon-Coral, 2017;Pecreaux et al, 2016). However, the oocytes of most organisms eliminate centrioles during their growth phase, and thus, meiotic spindles lack canonical centrosomes and only have a few or no astral microtubules (Sathananthan et al, 2006;Schuh and Ellenberg, 2007;Szollosi et al, 1972).…”

Section: Spindle Migration During Meiosis Imentioning

confidence: 99%

Functions of actin in mouse oocytes at a glance

Uraji

Scheffler

Schuh

2018

Journal of Cell Science

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Gametes undergo a specialized and reductional cell division termed meiosis. Female gametes (oocytes) undergo two rounds of meiosis; the first meiotic division produces the fertilizable egg, while the second meiotic division occurs upon fertilization. Both meiotic divisions are highly asymmetric, producing a large egg and small polar bodies. Actin takes over various essential function during oocyte meiosis, many of which commonly rely on microtubules in mitotic cells. Specifically, the actin network has been linked to longrange vesicle transport, nuclear positioning, spindle migration and anchorage, polar body extrusion and accurate chromosome segregation in mammalian oocytes. In this Cell Science at a Glance article and the accompanying poster, we summarize the many functions of the actin cytoskeleton in oocytes, with a focus on findings from the mouse model system.

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“…Large-scale reorganization of the microtubule (MT) cytoskeleton is essential for a variety of processes, such as cell division, differentiation and polarization. In dividing cells, a balance of dynein-dependent pulling forces and MT pushing forces determines the positioning of the MTbased mitotic spindle (Howard and Garzon-Coral, 2017;Kotak and Gonczy, 2013). In interphase cells with dense, non-centrosomal MT arrays, such as epithelial or neuronal cells, polarization is a slow process that requires hours, if not days (reviewed in (Kapitein and Hoogenraad, 2015;Meiring et al, 2020)).…”

Section: Introductionmentioning

confidence: 99%

Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

Hooikaas

Damstra

Gros

et al. 2020

Preprint

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When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome towards the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of microtubule dynamics contributes to this process. Here, we show that the knockout of KIF21B, a kinesin-4 linked to autoimmune disorders, causes microtubule overgrowth and perturbs centrosome translocation. KIF21B restricts microtubule length by inducing microtubule pausing typically followed by catastrophe. Catastrophe induction with vinblastine prevented microtubule overgrowth and was sufficient to rescue centrosome polarization in KIF21B-knockout cells. Biophysical simulations showed that a relatively small number of KIF21B molecules can restrict microtubule length and promote an imbalance of dynein-mediated pulling forces that allows the centrosome to translocate past the nucleus. We conclude that proper control of microtubule length is important for allowing rapid remodeling of the cytoskeleton and efficient T cell polarization.

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Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces

Cited by 44 publications

References 106 publications

Emergence of Embryo Shape During Cleavage Divisions

Emergence of Embryo Shape During Cleavage Divisions

Functions of actin in mouse oocytes at a glance

Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

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