Topics

Cell shape and intercellular adhesion regulate mitotic spindle orientation.

08:00 EDT 14th August 2019 | BioPortfolio

Summary of "Cell shape and intercellular adhesion regulate mitotic spindle orientation."

Cell division orientation plays an essential role in tissue morphogenesis and cell fate decision. Recent studies showed that either cell shape or adhesion geometry can regulate the orientation of mitotic spindles, and thereby the cell division orientation. However, how they together regulate the spindle orientation remains largely unclear. In this work, we use a general computational model to investigate the competitive mechanism of determining the spindle orientation between cell shape and intercellular adhesion in epithelial cells. We find the spindle orientation is dominated by the intercellular adhesion when the cell shape anisotropy is small, but dominated by the cell shape when the shape anisotropy is large. A strong adhesion and moderate adhesive size can ensure the planar division of epithelial cells with large apico-basal elongation. We also find the spindle orientation could be perpendicular to the adhesive region when only one side of the cell is adhered to E-cadherin-coated matrix. But after the cell is compressed, the spindle orientation is governed by the cell shape and the spindle will be parallel to the adhesive region when the cell shape anisotropy is large. Finally, we demonstrate the competition between cell shape and tricellular junctions can also effectively regulate the spindle orientation. Movie S1 Movie S1 Positioning and orientation of simulated spindles in round cells without adhesion. Several examples show that the spindles in round cells without adhesion can always be positioned to the cell center from random initial conditions in the simulations, but the spindle orientation is randomly distributed since the cell shape and the cortical parameters are isotropic. The cell diameter is 20 µm. Movie S2 Movie S2 Positioning and orientation of simulated spindles in stretched-shaped cells without adhesion. In the cells with the stadium shape (left) or the elliptical shape (right), the spindles can always be positioned to the cell center and oriented along the long axis of the cell shape from random initial conditions in the simulations. The aspect ratio of the shape are all 1.5, and the area is the same as the 20 µm-diameter round cell. Two examples are provided for each shape. Movie S3 Movie S3 Orientation of simulated spindles in the cells with bilateral symmetric adhesion and various aspect ratios of the stadium shape. The stadium-shaped cells have the bilateral symmetric adhesion (red marked) whose parameters are k=11 and L=12 µm, and the aspect ratio is given as λ=1, 1.2, 1.4, or 2. In these cases, the stable spindle orientation transits from the horizontal to the orthogonal direction with the increase of the cell aspect ratio as the cell area is constant. Movie S4 Movie S4 Orientation of simulated spindles in the cells with unilateral adhesion and various aspect ratios of the stadium shape. The stadium-shaped cells have the unilateral adhesion (red marked) whose parameters are k=11 and that L increases with the aspect ratio, and the aspect ratio is given as λ=1, 1.2, 1.5, or 2. In these cases, the stable spindle orientation transits from the perpendicular to the parallel direction to the adhesion region with the increase of the cell aspect ratio. Movie S5 Movie S5 Orientation of simulated spindles in typical polygonal cells with and without the mechanism of tricellular junctions. Two typical cell shapes are selected, in which the tricellular junction polarity (red dotted) and the cell shape polarity are consistent and inconsistent, respectively. The simulated spindle can orient along the cell shape polarity without the tricellular junction mechanism, but along the tricellular junction polarity with the tricellular junction mechanism. Movie S6 Movie S6 Orientation of simulated spindles in the cells with tricellular junctions and various aspect ratios of the stadium shape. The stadium-shaped cells have the tricellular junctions (red dotted), and the aspect ratio is given as λ=1.2 or 1.8. In these cases, the stable spindle orientation transits from the tricellular junction polarity to the cell shape polarity with the increase of the cell aspect ratio as the cell area is constant.

Affiliation

Journal Details

This article was published in the following journal.

Name: Molecular biology of the cell
ISSN: 1939-4586
Pages: mbcE19040227

Links

DeepDyve research library

PubMed Articles [20720 Associated PubMed Articles listed on BioPortfolio]

How to tune spindle size relative to cell size?

Cells need to regulate the size and shape of their organelles for proper function. For example, the mitotic spindle adapts its size to changes in cell size over several orders of magnitude, but we lac...

NDP52 tunes cortical actin interaction with astral microtubules for accurate spindle orientation.

Oriented cell divisions are controlled by a conserved molecular cascade involving Gαi, LGN, and NuMA. Here, we show that NDP52 regulates spindle orientation via remodeling the polar cortical actin cy...

Bisphenol A disrupts mitotic progression via disturbing spindle attachment to kinetochore and centriole duplication in cancer cell lines.

Bisphenol A [BPA, 2,2-bis-(4-hydroxyphenyl)propane] is one of the most prevalent synthetic environmental estrogens; as an endocrine disruptor, it is associated with endocrine-related cancers including...

Viral Infection or IFN-α Alters Mitotic Spindle Orientation by Modulating Pericentrin Levels.

Congenital microcephaly occurs in utero during Zika virus (ZIKV) infection. The single-gene disorder, Majewski osteodysplastic primordial dwarfism type II (MOPDII), also leads to microcephaly and is c...

Centrosomal Actin Assembly Is Required for Proper Mitotic Spindle Formation and Chromosome Congression.

Cytoskeletal cross talk between actin filaments and microtubules is a common mechanism governing the assembly of cellular structures, i.e., during filopodia formation or cilia organization. However, p...

Clinical Trials [8213 Associated Clinical Trials listed on BioPortfolio]

A Phase II Study of AZD4877 (a Novel Anti-mitotic Agent) in Advanced Bladder Cancer

The purpose of this Phase II study is to determine if AZD4877, an experimental drug that is a novel anti-mitotic agent (Eg5 or Kinesin Spindle Protein inhibitor that interferes with tumor...

Simvastatin Reduces Circulating Osteoprotegerin Levels in Patients With Type 2 Diabetes

Diabetes is associated with dyslipidaemia leading to generalized atherosclerosis, cardiovascular disease (CVD) and nephropathy. Osteoprotegerin (OPG), a glycoprotein involved in bone homeo...

Vinorelbine in Advanced BRAF-like Colon Cancer

Vecchione et al showed that suppression of RANBP2 results in mitotic defects only in BRAF-like colon cancer (CC) cells, which leads to cell death. Mechanistically, RANBP2 silencing reduces...

Sitagliptin Therapy and Kinetics of Inflammatory Markers

Inflammatory processes are increasingly being recognized as a critical step in the pathogenesis of both diabetes and heart disease and may constitute a biological link between the two dise...

Oocyte Cryopreservation: The Impact of Cryopreservation on the Meiotic Spindle and Mitochondria of Human Oocytes.

Our aims is to document the possible effect of cryo- preservation at the meiotic spindle and mitochondrial levels.

Medical and Biotech [MESH] Definitions

The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).

A cell-surface ligand involved in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue.

A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.

Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.

The first phase of cell nucleus division, in which the CHROMOSOMES become visible, the CELL NUCLEUS starts to lose its identity, the MITOTIC SPINDLE APPARATUS appears, and the CENTRIOLES migrate toward opposite poles.

Quick Search


DeepDyve research library

Searches Linking to this Article