scholarly journals Isotropic myosin-generated tissue tension is required for the dynamic orientation of the mitotic spindle

2020 ◽  
Vol 31 (13) ◽  
pp. 1370-1379 ◽  
Author(s):  
Maxine S. Y. Lam ◽  
Ana Lisica ◽  
Nitya Ramkumar ◽  
Ginger Hunter ◽  
Yanlan Mao ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Orientation ◽  
Cell Axis ◽  
Tissue Tension

By studying the dynamics of spindle orientation in mechanically distinct regions of an epithelium, this article reveals a role for isotropic tension in aiding accurate alignment of the spindle with the long cell axis.

scholarly journals Isotropic myosin-generated tissue tension is required for the dynamic orientation of the mitotic spindle

2018 ◽  
Author(s):  
Maxine SY Lam ◽  
Ana Lisica ◽  
Nitya Ramkumar ◽  
Yanlan Mao ◽  
Guillaume Charras ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Myosin Ii ◽  
Spindle Orientation ◽  
Genetic Screens ◽  
Cell Axis ◽  
Division Plane ◽  
Stable Substrate ◽  
Muscle Myosin ◽  
Tissue Tension ◽  
Do So

ABSTRACTThe ability of epithelial cells to divide along their long cell axis, known as “Hertwig’s rule”, has been proposed to play an important and wide-ranging role in homogenising epithelial cell packing during tissue development and homeostasis. Since the position of the anaphase spindle defines the division plane, how divisions are oriented requires an understanding of the mechanisms that position the mitotic spindle. While many of the molecules required to orient the mitotic spindle have been identified in genetic screens, the mechanisms by which spindles read and align with the long cell axis remain poorly understood. Here, in exploring the dynamics of spindle orientation in mechanically distinct regions of the fly notum, we find that the ability of cells to properly orient their divisions depends both on cortical cues and on local tissue tension. Thus, spindles align with the long cell axis in tissues in which isotropic tension is elevated, but fail to do so in elongated cells within the crowded midline, where tension is low. Importantly, these region-specific differences in spindle behaviour can be reversed by decreasing or increasing the activity of non-muscle Myosin II. In addition, spindles in a tissue experiencing isotropic stress fail to align with the long cell axis if cells are mechanically isolated from their neighbours. These data lead us to propose that isotropic tension is required within an epithelium to provide cells with a mechanically stable substrate upon which localised cortical Dynein can pull on astral microtubules to orient the spindle.

scholarly journals Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation

PLoS Biology ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. e3000531 ◽  
Author(s):  
Changsen Leng ◽  
Arend W. Overeem ◽  
Fernando Cartón-Garcia ◽  
Qinghong Li ◽  
Karin Klappe ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Late Endosome ◽  
Spindle Orientation

scholarly journals NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lindsey Seldin ◽  
Andrew Muroyama ◽  
Terry Lechler
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Spindle Orientation ◽  
Direct Function ◽  
Spindle Positioning ◽  
Adult Mice ◽  
Neonatal Lethality ◽  
The Matrix

Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical dynein/dynactin was sufficient to generate forces on astral microtubules (MTs) to orient the spindle, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation establishment in keratinocytes and that NuMA’s MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions in skin caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. In addition, we show that NuMA-MT interactions are also required in adult mice for hair follicle morphogenesis and spindle orientation within the transit-amplifying cells of the matrix. Loss of spindle orientation in matrix cells results in defective differentiation of matrix-derived lineages. Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures.

scholarly journals Warts Phosphorylates Mud to Promote Pins-Mediated Mitotic Spindle Orientation in Drosophila , Independent of Yorkie

2015 ◽  
Vol 25 (21) ◽  
pp. 2751-2762 ◽  
Author(s):  
Evan B. Dewey ◽  
Desiree Sanchez ◽  
Christopher A. Johnston
Keyword(s):  
Mitotic Spindle ◽  
Spindle Orientation

scholarly journals PTEN controls glandular morphogenesis through a juxtamembrane β-Arrestin1/ARHGAP21 scaffolding complex

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Arman Javadi ◽  
Ravi K Deevi ◽  
Emma Evergren ◽  
Elodie Blondel-Tepaz ◽  
George S Baillie ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Molecular Mechanisms ◽  
Regulatory Protein ◽  
Membrane Binding ◽  
Three Dimensional ◽  
Spindle Orientation ◽  
C2 Domain ◽  
Gtpase Activating Protein ◽  
Defective Mutant ◽  
Glandular Morphogenesis

PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signaling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42 -dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here, we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis. Effects of PTEN deficiency were phenocopied by β-Arrestin1 KD or inhibition of β-Arrestin1-ARHGAP21 interactions. Conversely, silencing of ARHGAP21 enhanced Cdc42 activation and rescued aberrant morphogenic processes of PTEN-deficient cultures. Expression of the PTEN C2 domain mimicked effects of full-length PTEN but a membrane-binding defective mutant of the C2 domain abrogated these properties. Our results show that PTEN controls multicellular assembly through a membrane-associated regulatory protein complex composed of β-Arrestin1, ARHGAP21 and Cdc42.

Phosphorylation of BACH1 switches its function from transcription factor to mitotic chromosome regulator and promotes its interaction with HMMR

2018 ◽  
Vol 475 (5) ◽  
pp. 981-1002 ◽  
Author(s):  
Jie Li ◽  
Hiroki Shima ◽  
Hironari Nishizawa ◽  
Masatoshi Ikeda ◽  
Andrey Brydun ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Isotope Labeling ◽  
Binding Activity ◽  
Mass Spectrometry Analysis ◽  
Spindle Orientation ◽  
Mitotic Spindles ◽  
Spectrometry Analysis ◽  
Dna Binding Activity ◽  
Ejection Force ◽  
M Phase

The transcription repressor BACH1 performs mutually independent dual roles in transcription regulation and chromosome alignment during mitosis by supporting polar ejection force of mitotic spindle. We now found that the mitotic spindles became oblique relative to the adhesion surface following endogenous BACH1 depletion in HeLa cells. This spindle orientation rearrangement was rescued by re-expression of BACH1 depending on its interactions with HMMR and CRM1, both of which are required for the positioning of mitotic spindle, but independently of its DNA-binding activity. A mass spectrometry analysis of BACH1 complexes in interphase and M phase revealed that BACH1 lost during mitosis interactions with proteins involved in chromatin and gene expression but retained interactions with HMMR and its known partners including CHICA. By analyzing BACH1 modification using stable isotope labeling with amino acids in cell culture, mitosis-specific phosphorylations of BACH1 were observed, and mutations of these residues abolished the activity of BACH1 to restore mitotic spindle orientation in knockdown cells and to interact with HMMR. Detailed histological analysis of Bach1-deficient mice revealed lengthening of the epithelial fold structures of the intestine. These observations suggest that BACH1 performs stabilization of mitotic spindle orientation together with HMMR and CRM1 in mitosis, and that the cell cycle-specific phosphorylation switches the transcriptional and mitotic functions of BACH1.

scholarly journals Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium

2019 ◽  
Vol 132 (10) ◽  
pp. jcs223313 ◽  
Author(s):  
D. Bazzoun ◽  
H. A. Adissu ◽  
L. Wang ◽  
A. Urazaev ◽  
I. Tenvooren ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Connexin 43 ◽  
Spindle Orientation ◽  
Breast Epithelium ◽  
Tissue Polarity

scholarly journals LGN regulates mitotic spindle orientation during epithelial morphogenesis

2010 ◽  
Vol 189 (2) ◽  
pp. 275-288 ◽  
Author(s):  
Zhen Zheng ◽  
Huabin Zhu ◽  
Qingwen Wan ◽  
Jing Liu ◽  
Zhuoni Xiao ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Mdck Cells ◽  
Apical Cell ◽  
Cell Polarization ◽  
Epithelial Morphogenesis ◽  
Spindle Orientation ◽  
Cell Cortex ◽  
Dividing Cells ◽  
Cortical Localization ◽  
Lateral Cell

Coordinated cell polarization and mitotic spindle orientation are thought to be important for epithelial morphogenesis. Whether spindle orientation is indeed linked to epithelial morphogenesis and how it is controlled at the molecular level is still unknown. Here, we show that the NuMA- and Gα-binding protein LGN is required for directing spindle orientation during cystogenesis of MDCK cells. LGN localizes to the lateral cell cortex, and is excluded from the apical cell cortex of dividing cells. Depleting LGN, preventing its cortical localization, or disrupting its interaction with endogenous NuMA or Gα proteins all lead to spindle misorientation and abnormal cystogenesis. Moreover, artificial mistargeting of endogenous LGN to the apical membrane results in a near 90° rotation of the spindle axis and profound cystogenesis defects that are dependent on cell division. The normal apical exclusion of LGN during mitosis appears to be mediated by atypical PKC. Thus, cell polarization–mediated spatial restriction of spindle orientation determinants is critical for epithelial morphogenesis.

scholarly journals Eph signaling controls mitotic spindle orientation and cell proliferation in neuroepithelial cells

2019 ◽  
Vol 218 (4) ◽  
pp. 1200-1217 ◽  
Author(s):  
Maribel Franco ◽  
Ana Carmena
Keyword(s):  
Cell Proliferation ◽  
Cell Fate ◽  
Mitotic Spindle ◽  
Optic Lobe ◽  
Spindle Orientation ◽  
Intercellular Signaling ◽  
Neuroepithelial Cells ◽  
Core Components ◽  
Conserved Core ◽  
Activity Dependent

Mitotic spindle orientation must be tightly regulated during development and adult tissue homeostasis. It determines cell-fate specification and tissue architecture during asymmetric and symmetric cell division, respectively. Here, we uncover a novel role for Ephrin–Eph intercellular signaling in controlling mitotic spindle alignment in Drosophila optic lobe neuroepithelial cells through aPKC activity–dependent myosin II regulation. We show that conserved core components of the mitotic spindle orientation machinery, including Discs Large1, Mud/NuMA, and Canoe/Afadin, mislocalize in dividing Eph mutant neuroepithelial cells and produce spindle alignment defects in these cells when they are down-regulated. In addition, the loss of Eph leads to a Rho signaling–dependent activation of the PI3K–Akt1 pathway, enhancing cell proliferation within this neuroepithelium. Hence, Eph signaling is a novel extrinsic mechanism that regulates both spindle orientation and cell proliferation in the Drosophila optic lobe neuroepithelium. Similar mechanisms could operate in other Drosophila and vertebrate epithelia.

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