Spindle orientation: a question of complex positioning

Bergstralh, Daniel T.; Dawney, Nicole S; Johnston, Daniel St

doi:10.1242/dev.140764

Cited by 93 publications

(93 citation statements)

References 122 publications

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“…targeting mig-5 and dsh-2 resulted in embryonic lethality in all treated embryos 668 divisions is limited to a handful of contexts, and the generality of these 682 mechanisms is unknown Bergstralh et al, 2017). 683…”

Section: Dishevelled Is Required For Apr-1/apc Polarization 650mentioning

confidence: 99%

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A CRISPR Tagging-Based Screen Reveals Localized Players in Wnt-Directed Asymmetric Cell Division

et al. 2018

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Oriented cell divisions are critical to establish and maintain cell fates and tissue organization. Diverse extracellular and intracellular cues have been shown to provide spatial information for mitotic spindle positioning; however, the molecular mechanisms by which extracellular signals communicate with cells to direct mitotic spindle positioning are largely unknown. In animal cells, oriented cell divisions are often achieved by the localization of force-generating motor protein complexes to discrete cortical domains. Disrupting either these force-generating complexes or proteins that globally affect microtubule stability results in defects in mitotic positioning, irrespective of whether these proteins function as spatial cues for spindle orientation. This poses a challenge to traditional genetic dissection of this process. Therefore, as an alternative strategy to identify key proteins that act downstream of intercellular signaling, we screened the localization of many candidate proteins by inserting fluorescent tags directly into endogenous gene loci, without overexpressing the proteins. We tagged 23 candidate proteins in Caenorhabditis elegans and examined each protein’s localization in a well-characterized, oriented cell division in the four-cell-stage embryo. We used cell manipulations and genetic experiments to determine which cells harbor key localized proteins and which signals direct these localizations in vivo. We found that Dishevelled and adenomatous polyposis coli homologs are polarized during this oriented cell division in response to a Wnt signal, but two proteins typically associated with mitotic spindle positioning, homologs of NuMA and Dynein, were not detectably polarized. These results suggest an unexpected mechanism for mitotic spindle positioning in this system, they pinpoint key proteins of interest, and they highlight the utility of a screening approach based on analyzing the localization of endogenously tagged proteins.

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Section: Dishevelled Is Required For Apr-1/apc Polarization 650mentioning

confidence: 99%

“…Intercellular signaling has been shown to regulate mitotic spindle 130 positioning through the enrichment of members of this complex to discrete 131 domains of the cell cortex (Bergstralh et al, 2017). For example, in Drosophila 132 sensory organ precursors, Planar Cell Polarity pathway members Frizzled and 133…”

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confidence: 99%

A CRISPR Tagging-Based Screen Reveals Localized Players in Wnt-Directed Asymmetric Cell Division

et al. 2018

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“…We further examined whether ALIX controls MS orientation in non‐stem cells by using two powerful Drosophila epithelial cell model systems for studying MS orientation during either asymmetric or symmetric planar cell division: (i) the Drosophila sensory organ precursor (SOP) cells of the pupal notum and (ii) the Drosophila follicle epithelial cells (FECs), respectively (Morin & Bellaiche, ; Bergstralh et al , ). First, we investigated the rotation of the MS in pupal SOPs as illustrated schematically in Fig F.…”

Section: Resultsmentioning

confidence: 99%

“…Drosophila FECs undergo planar, symmetric cell division to ensure formation of a monolayer of cells constituting the epithelium (Bergstralh et al , ). This is accomplished by orienting the MS parallel to the apical membrane, implying that the relative spindle angle between the polarity and MS axis is ideally 90° (illustrated in Fig B).…”

Section: Resultsmentioning

confidence: 99%

Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics

et al. 2018

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The orientation of the mitotic spindle (MS) is tightly regulated, but the molecular mechanisms are incompletely understood. Here we report a novel role for the multifunctional adaptor protein ALG-2-interacting protein X (ALIX) in regulating MS orientation in addition to its well-established role in cytokinesis. We show that ALIX is recruited to the pericentriolar material (PCM) of the centrosomes and promotes correct orientation of the MS in asymmetrically dividing stem cells and epithelial cells and symmetrically dividing and human epithelial cells. ALIX-deprived cells display defective formation of astral microtubules (MTs), which results in abnormal MS orientation. Specifically, ALIX is recruited to the PCM via Spindle defective 2 (DSpd-2)/Cep192, where ALIX promotes accumulation of γ-tubulin and thus facilitates efficient nucleation of astral MTs. In addition, ALIX promotes MT stability by recruiting microtubule-associated protein 1S (MAP1S), which stabilizes newly formed MTs. Altogether, our results demonstrate a novel evolutionarily conserved role of ALIX in providing robustness to the orientation of the MS by promoting astral MT formation during asymmetric and symmetric cell division.

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“…It is only at the beginning of anaphase when MAs are displaced to eccentric positions. Based on these observations, it is envisioned that this cortical spindle‐orienting machinery as demonstrated in model organisms such as C. elegans (nematode) and Drosophila (fruit fly) is established during metaphase at the sites where smaller daughter cells will be given off (Bergstralh, Dawney, & St Johnston, ; Lu & Johnston, ). Moreover, during anaphase, it would exert a pulling force on astral microtubules to move the spindle toward the cortical site of the machinery.…”

Section: Discussionmentioning

confidence: 99%

The cleavage program in the 2d cell lineage of Tubifex embryos

Yoshida

Arai

Aoki

et al. 2019

Journal of Morphology

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Early development in clitellate annelids is characterized by a highly stereotyped sequence of unequal, spiral cleavages. Cell 2d (i.e., the second micromere of the D quadrant) in the oligochaete Tubifex tubifex also undergoes an evolutionarily conserved sequence of cell division to produce four bilateral pairs of ectodermal teloblasts that act as embryonic stem cells. This study was conducted to characterize each of the 15 rounds of cell division that occur in the 2d cell lineage in this clitellate. After its occurrence, cell 2d undergoes three rounds of highly unequal divisions, giving off the first smaller daughter cell toward the posterior right of the larger daughter cell, the second cell toward the posterior left, and the third cell toward the anterior side of the cell; the larger daughter cell that results from the third division (i.e., the great‐granddaughter cell of 2d) then divides equally into a bilateral pair of NOPQ proteloblasts. Cell NOPQ on either side of the embryo undergoes 11 rounds of cell division, during which ectoteloblasts N, Q, and O/P are produced in this order. After its appearance, NOPQ undergoes highly unequal divisions twice cutting off the smaller cells toward the anterior end of the embryo and then divides almost equally into ectoteloblast N and proteloblast OPQ. After its appearance, OPQ undergoes highly unequal divisions twice giving off the first smaller cell toward the anterior and the second smaller cell toward the posterior of the embryo and then divides almost equally into ectoteloblast Q and proteloblast OP. Finally, OP undergoes highly unequal division four times after its birth budding off the smaller cells toward the anterior and then cleaves equally into ectoteloblasts O and P. In the unequally dividing cells of the 2d cell lineage, the mitotic apparatus (MA), which forms at the cell's center, moves eccentrically toward the cortical site where the smaller cell will be given off. The moving MA is oriented perpendicular to the surface it approaches, and its peripheral pole becomes closely associated with the cell cortex. In contrast, the MA involved in the equal divisions remains in the cell center throughout mitosis. The key features of the cleavage program in the 2d cell lineage are discussed in light of the present observations. The mechanical aspects of unequal cleavage in the 2d cell lineage and the modes of specification of MA orientation are discussed. A comparison of the cleavage mode in the 2d cell lineage is also performed among six selected clitellate annelid species.

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Spindle orientation: a question of complex positioning

Cited by 93 publications

References 122 publications

A CRISPR Tagging-Based Screen Reveals Localized Players in Wnt-Directed Asymmetric Cell Division

A CRISPR Tagging-Based Screen Reveals Localized Players in Wnt-Directed Asymmetric Cell Division

Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics

The cleavage program in the 2d cell lineage of Tubifex embryos

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