scholarly journals Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ognjen Golub ◽  
Brett Wee ◽  
Rhonda A Newman ◽  
Nicole M Paterson ◽  
Kenneth E Prehoda
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Intramolecular Interaction ◽  
Spindle Orientation ◽  
Orientation Factor ◽  
Daughter Cells ◽  
Kinase C ◽  
Discs Large ◽  
Fate Determinants

Asymmetric division generates cellular diversity by producing daughter cells with different fates. In animals, the mitotic spindle aligns with Par complex polarized fate determinants, ensuring that fate determinant cortical domains are bisected by the cleavage furrow. Here, we investigate the mechanisms that couple spindle orientation to polarity during asymmetric cell division of Drosophila neuroblasts. We find that the tumor suppressor Discs large (Dlg) links the Par complex component atypical Protein Kinase C (aPKC) to the essential spindle orientation factor GukHolder (GukH). Dlg is autoinhibited by an intramolecular interaction between its SH3 and GK domains, preventing Dlg interaction with GukH at cortical sites lacking aPKC. When co-localized with aPKC, Dlg is phosphorylated in its SH3 domain which disrupts autoinhibition and allows GukH recruitment by the GK domain. Our work establishes a molecular connection between the polarity and spindle orientation machineries during asymmetric cell division.

scholarly journals Robust control of mitotic spindle orientation in the developing epidermis

2010 ◽  
Vol 191 (5) ◽  
pp. 915-922 ◽  
Author(s):  
Nicholas D. Poulson ◽  
Terry Lechler
Keyword(s):  
Cell Division ◽  
Robust Control ◽  
Progenitor Cells ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Transcriptional Regulator ◽  
Spindle Orientation ◽  
Control Points ◽  
External Cues ◽  
Increase Surface Area

Progenitor cells must balance self-amplification and production of differentiated progeny during development and homeostasis. In the epidermis, progenitors divide symmetrically to increase surface area and asymmetrically to promote stratification. In this study, we show that individual epidermal cells can undergo both types of division, and therefore, the balance is provided by the sum of individual cells’ choices. In addition, we define two control points for determining a cell’s mode of division. First is the expression of the mouse Inscuteable gene, which is sufficient to drive asymmetric cell division (ACD). However, there is robust control of division orientation as excessive ACDs are prevented by a change in the localization of NuMA, an effector of spindle orientation. Finally, we show that p63, a transcriptional regulator of stratification, does not control either of these processes. These data have uncovered two important regulatory points controlling ACD in the epidermis and allow a framework for analysis of how external cues control this important choice.

scholarly journals Asymmetric cell division: microtubule dynamics and spindle asymmetry

2002 ◽  
Vol 115 (11) ◽  
pp. 2257-2264 ◽  
Author(s):  
Julia A. Kaltschmidt ◽  
Andrea H. Brand
Keyword(s):  
Cell Division ◽  
Cell Size ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Model Organisms ◽  
Complex Nature ◽  
Daughter Cells ◽  
Cytoskeletal Dynamics ◽  
Insight Into

Asymmetric cell division can produce daughter cells with different developmental fates and is often accompanied by a difference in cell size. A number of recent genetic and in vivo imaging studies in Drosophilaand Caenorhabditis elegans have begun to elucidate the mechanisms underlying the rearrangements of the cytoskeleton that result in eccentrically positioned cleavage planes. As a result, we are starting to gain an insight into the complex nature of the signals controlling cytoskeletal dynamics in the dividing cell. In this commentary we discuss recent findings on how the mitotic spindle is positioned and on cleavage site induction and place them in the context of cell size asymmetry in different model organisms.

scholarly journals Epithelial polarity and spindle orientation: intersecting pathways

2013 ◽  
Vol 368 (1629) ◽  
pp. 20130291 ◽  
Author(s):  
Dan T. Bergstralh ◽  
Timm Haack ◽  
Daniel St Johnston
Keyword(s):  
Epithelial Cells ◽  
Cell Fate ◽  
Spindle Orientation ◽  
Mitotic Spindles ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Discs Large ◽  
Stem Cell Divisions ◽  
Fate Determinants ◽  
Cell Fate Determinants

During asymmetric stem cell divisions, the mitotic spindle must be correctly oriented and positioned with respect to the axis of cell polarity to ensure that cell fate determinants are appropriately segregated into only one daughter cell. By contrast, epithelial cells divide symmetrically and orient their mitotic spindles perpendicular to the main apical–basal polarity axis, so that both daughter cells remain within the epithelium. Work in the past 20 years has defined a core ternary complex consisting of Pins, Mud and Gαi that participates in spindle orientation in both asymmetric and symmetric divisions. As additional factors that interact with this complex continue to be identified, a theme has emerged: there is substantial overlap between the mechanisms that orient the spindle and those that establish and maintain apical–basal polarity in epithelial cells. In this review, we examine several factors implicated in both processes, namely Canoe, Bazooka, aPKC and Discs large, and consider the implications of this work on how the spindle is oriented during epithelial cell divisions.

scholarly journals Specific polar subpopulations of astral microtubules control spindle orientation and symmetric neural stem cell division

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Felipe Mora-Bermúdez ◽  
Fumio Matsuzaki ◽  
Wieland B Huttner
Keyword(s):  
Cell Division ◽  
Basal Cell ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Spindle Cell ◽  
Spindle Orientation ◽  
Cell Cortex ◽  
Dividing Cells ◽  
Stem Cell Division

Mitotic spindle orientation is crucial for symmetric vs asymmetric cell division and depends on astral microtubules. Here, we show that distinct subpopulations of astral microtubules exist, which have differential functions in regulating spindle orientation and division symmetry. Specifically, in polarized stem cells of developing mouse neocortex, astral microtubules reaching the apical and basal cell cortex, but not those reaching the central cell cortex, are more abundant in symmetrically than asymmetrically dividing cells and reduce spindle orientation variability. This promotes symmetric divisions by maintaining an apico-basal cleavage plane. The greater abundance of apical/basal astrals depends on a higher concentration, at the basal cell cortex, of LGN, a known spindle-cell cortex linker. Furthermore, newly developed specific microtubule perturbations that selectively decrease apical/basal astrals recapitulate the symmetric-to-asymmetric division switch and suffice to increase neurogenesis in vivo. Thus, our study identifies a novel link between cell polarity, astral microtubules, and spindle orientation in morphogenesis.

Frizzled regulates localization of cell-fate determinants and mitotic spindle rotation during asymmetric cell division

2000 ◽  
Vol 3 (1) ◽  
pp. 50-57 ◽  
Author(s):  
Yohanns Bellaïche ◽  
Michel Gho ◽  
Julia A. Kaltschmidt ◽  
Andrea H. Brand ◽  
François Schweisguth
Keyword(s):  
Cell Division ◽  
Cell Fate ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Spindle Rotation ◽  
Fate Determinants ◽  
Cell Fate Determinants

scholarly journals Asymmetric cell division-dominant neutral drift model for normal intestinal stem cell homeostasis

2019 ◽  
Vol 316 (1) ◽  
pp. G64-G74 ◽  
Author(s):  
Yoshitatsu Sei ◽  
Jianying Feng ◽  
Carson C. Chow ◽  
Stephen A. Wank
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Dominant Mode ◽  
Lineage Tracing ◽  
Intestinal Stem Cells ◽  
In Vivo Studies ◽  
Neutral Drift ◽  
Drift Model

The normal intestinal epithelium is continuously regenerated at a rapid rate from actively cycling Lgr5-expressing intestinal stem cells (ISCs) that reside at the crypt base. Recent mathematical modeling based on several lineage-tracing studies in mice shows that the symmetric cell division-dominant neutral drift model fits well with the observed in vivo growth of ISC clones and suggests that symmetric divisions are central to ISC homeostasis. However, other studies suggest a critical role for asymmetric cell division in the maintenance of ISC homeostasis in vivo. Here, we show that the stochastic branching and Moran process models with both a symmetric and asymmetric division mode not only simulate the stochastic growth of the ISC clone in silico but also closely fit the in vivo stem cell dynamics observed in lineage-tracing studies. In addition, the proposed model with highest probability for asymmetric division is more consistent with in vivo observations reported here and by others. Our in vivo studies of mitotic spindle orientations and lineage-traced progeny pairs indicate that asymmetric cell division is a dominant mode used by ISCs under normal homeostasis. Therefore, we propose the asymmetric cell division-dominant neutral drift model for normal ISC homeostasis. NEW & NOTEWORTHY The prevailing mathematical model suggests that intestinal stem cells (ISCs) divide symmetrically. The present study provides evidence that asymmetric cell division is the major contributor to ISC maintenance and thus proposes an asymmetric cell division-dominant neutral drift model. Consistent with this model, in vivo studies of mitotic spindle orientation and lineage-traced progeny pairs indicate that asymmetric cell division is the dominant mode used by ISCs under normal homeostasis.

scholarly journals Asymmetric Cell Division in Polyploid Giant Cancer Cells and Low Eukaryotic Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Dan Zhang ◽  
Yijia Wang ◽  
Shiwu Zhang
Keyword(s):  
Cell Division ◽  
Cancer Cells ◽  
Cobalt Chloride ◽  
Asymmetric Cell Division ◽  
Cell Polarization ◽  
Daughter Cells ◽  
Evolutionarily Conserved ◽  
Polyploid Giant Cancer Cells ◽  
Cell Diversity ◽  
Eukaryotic Organisms

Asymmetric cell division is critical for generating cell diversity in low eukaryotic organisms. We previously have reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride demonstrate the ability to use an evolutionarily conserved process for renewal and fast reproduction, which is normally confined to simpler organisms. The budding yeast,Saccharomyces cerevisiae, which reproduces by asymmetric cell division, has long been a model for asymmetric cell division studies. PGCCs produce daughter cells asymmetrically in a manner similar to yeast, in that both use budding for cell polarization and cytokinesis. Here, we review the results of recent studies and discuss the similarities in the budding process between yeast and PGCCs.

Sign in / Sign up

Export Citation Format

Share Document