scholarly journals To Divide or Invade: A Look Behind the Scenes of the Proliferation-Invasion Interplay in the Caenorhabditis elegans Anchor Cell

2021 ◽  
Vol 8 ◽  
Author(s):  
Evelyn Lattmann ◽  
Ting Deng ◽  
Alex Hajnal
Keyword(s):  
Cell Proliferation ◽  
Caenorhabditis Elegans ◽  
Cell Invasion ◽  
Malignant Tumors ◽  
Cell Types ◽  
Basement Membranes ◽  
The Body ◽  
C Elegans ◽  
Anchor Cell ◽  
Different Cell Types

Cell invasion is defined by the capability of cells to migrate across compartment boundaries established by basement membranes (BMs). The development of complex organs involves regulated cell growth and regrouping of different cell types, which are enabled by controlled cell proliferation and cell invasion. Moreover, when a malignant tumor takes control over the body, cancer cells evolve to become invasive, allowing them to spread to distant sites and form metastases. At the core of the switch between proliferation and invasion are changes in cellular morphology driven by remodeling of the cytoskeleton. Proliferative cells utilize their actomyosin network to assemble a contractile ring during cytokinesis, while invasive cells form actin-rich protrusions, called invadopodia that allow them to breach the BMs. Studies of developmental cell invasion as well as of malignant tumors revealed that cell invasion and proliferation are two mutually exclusive states. In particular, anchor cell (AC) invasion during Caenorhabditis elegans larval development is an excellent model to study the transition from cell proliferation to cell invasion under physiological conditions. This mini-review discusses recent insights from the C. elegans AC invasion model into how G1 cell-cycle arrest is coordinated with the activation of the signaling networks required for BM breaching. Many regulators of the proliferation-invasion network are conserved between C. elegans and mammals. Therefore, the worm may provide important clues to better understand cell invasion and metastasis formation in humans.

scholarly journals Roles of Actin in the Morphogenesis of the Early Caenorhabditis elegans Embryo

2020 ◽  
Vol 21 (10) ◽  
pp. 3652
Author(s):  
Dureen Samandar Eweis ◽  
Julie Plastino
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Asymmetric Cell Division ◽  
Cell Types ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Asymmetric Cell Divisions ◽  
C Elegans ◽  
Asymmetric Divisions ◽  
Different Cell Types

The cell shape changes that ensure asymmetric cell divisions are crucial for correct development, as asymmetric divisions allow for the formation of different cell types and therefore different tissues. The first division of the Caenorhabditis elegans embryo has emerged as a powerful model for understanding asymmetric cell division. The dynamics of microtubules, polarity proteins, and the actin cytoskeleton are all key for this process. In this review, we highlight studies from the last five years revealing new insights about the role of actin dynamics in the first asymmetric cell division of the early C. elegans embryo. Recent results concerning the roles of actin and actin binding proteins in symmetry breaking, cortical flows, cortical integrity, and cleavage furrow formation are described.

scholarly journals An expanded auxin-inducible degron toolkit for Caenorhabditis elegans

Genetics ◽  
2021 ◽  
Author(s):  
Guinevere Ashley ◽  
Tam Duong ◽  
Max T Levenson ◽  
Michael A Q Martinez ◽  
Londen C Johnsen ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Genome Editing ◽  
Fluorescent Protein ◽  
Cell Types ◽  
Single Copy ◽  
Fluorescent Reporter ◽  
C Elegans ◽  
Seam Cell ◽  
Anchor Cell ◽  
Endogenous Substrates

Abstract The auxin-inducible degron (AID) system has emerged as a powerful tool to conditionally deplete proteins in a range of organisms and cell types. Here, we describe a toolkit to augment the use of the AID system in Caenorhabditis elegans. We have generated a set of single-copy, tissue-specific (germline, intestine, neuron, muscle, pharynx, hypodermis, seam cell, anchor cell) and pan-somatic TIR1-expressing strains carrying a co-expressed blue fluorescent reporter to enable use of both red and green channels in experiments. These transgenes are inserted into commonly used, well-characterized genetic loci. We confirmed that our TIR1-expressing strains produce the expected depletion phenotype for several nuclear and cytoplasmic AID-tagged endogenous substrates. We have also constructed a set of plasmids for constructing repair templates to generate fluorescent protein::AID fusions through CRISPR/Cas9-mediated genome editing. These plasmids are compatible with commonly used genome editing approaches in the C. elegans community (Gibson or SapTrap assembly of plasmid repair templates or PCR-derived linear repair templates). Together these reagents will complement existing TIR1 strains and facilitate rapid and high-throughput fluorescent protein::AID tagging of genes. This battery of new TIR1-expressing strains and modular, efficient cloning vectors serves as a platform for straightforward assembly of CRISPR/Cas9 repair templates for conditional protein depletion.

scholarly journals Basal extrusion drives cell invasion and mechanical stripping of E-cadherin

2018 ◽  
Author(s):  
John Fadul ◽  
Gloria M. Slattum ◽  
Nadja M. Redd ◽  
Mauricio Franco Jin ◽  
Michael J. Redd ◽  
...  
Keyword(s):  
Cell Invasion ◽  
Apical Cell ◽  
Cell Types ◽  
The Body ◽  
Oncogenic Mutations ◽  
Apical Extrusion ◽  
Cell Densities ◽  
Apical Membranes ◽  
Different Cell Types ◽  
E Cadherin

Metastasis is the predominant reason that patients succumb to cancer, yet the mechanisms that drive initial tumor cell invasion are poorly understood. We previously discovered that crowding-induced apical extrusion drives most epithelial cell death, critical to maintaining constant cell densities. Oncogenic mutations can disrupt apical cell extrusion, instead causing masses to form and aberrant basal extrusion. Using transparent zebrafish epidermis to model simple epithelia, we can image invasion events live at high resolution. We find that KRas/p53-transformed cells form masses and, at completely independent sites, invade by basal extrusion. Basal extrusion also causes invading cells to simultaneously mechanically shed their entire apical membranes and E-cadherin. Once cells invade the underlying tissue, they migrate throughout the body, divide, enter the bloodstream, and become different cell types. KRas-transformation makes cells intrinsically invasive by increasing basal extrusion rates; collaborating mutations in p53 allow disseminated cells to survive at distant sites.

scholarly journals Extracellular-Vesicle-Based Coatings Enhance Bioactivity of Titanium Implants—SurfEV

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1445
Author(s):  
Taisa Nogueira Pansani ◽  
Thanh Huyen Phan ◽  
Qingyu Lei ◽  
Alexey Kondyurin ◽  
Bill Kalionis ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Titanium Surface ◽  
Wound Closure ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Tissue Growth ◽  
Titanium Implants ◽  
The Body ◽  
High Concentrations ◽  
And Migration

Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that immobilizing EVs on implant surfaces could potentially generate highly bioactive and cell-instructive surfaces that would enhance implant integration into the body. Such surfaces could address a critical limitation of current implants, which do not promote bone tissue formation or bond bone. Here, we developed bioactive titanium surface coatings (SurfEV) using two types of EVs: secreted by decidual mesenchymal stem cells (DEVs) and isolated from fermented papaya fluid (PEVs). For each EV type, we determined the size, morphology, and molecular composition. High concentrations of DEVs enhanced cell proliferation, wound closure, and migration distance of osteoblasts. In contrast, the cell proliferation and wound closure decreased with increasing concentration of PEVs. DEVs enhanced Ca/P deposition on the titanium surface, which suggests improvement in bone bonding ability of the implant (i.e., osteointegration). EVs also increased production of Ca and P by osteoblasts and promoted the deposition of mineral phase, which suggests EVs play key roles in cell mineralization. We also found that DEVs stimulated the secretion of secondary EVs observed by the presence of protruding structures on the cell membrane. We concluded that, by functionalizing implant surfaces with specialized EVs, we will be able to enhance implant osteointegration by improving hydroxyapatite formation directly at the surface and potentially circumvent aseptic loosening of implants.

A Deficiency Screen for Zygotic Loci Required for Establishment and Patterning of the Epidermis in Caenorhabditis elegans

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 185-206 ◽  
Author(s):  
Rebecca M Terns ◽  
Peggy Kroll-Conner ◽  
Jiangwen Zhu ◽  
Sooyoun Chung ◽  
Joel H Rothman
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Types ◽  
Epidermal Cells ◽  
Epidermal Differentiation ◽  
Apparent Effect ◽  
Internal Organs ◽  
C Elegans ◽  
Seam Cell ◽  
Genomic Regions ◽  
Caenorhabditis Elegans Genome

To identify genomic regions required for establishment and patterning of the epidermis, we screened 58 deficiencies that collectively delete at least ∼67% of the Caenorhabditis elegans genome. The epidermal pattern of deficiency homozygous embryos was analyzed by examining expression of a marker specific for one of the three major epidermal cell types, the seam cells. The organization of the epidermis and internal organs was also analyzed using a monoclonal antibody specific for epithelial adherens junctions. While seven deficiencies had no apparent effect on seam cell production, 21 were found to result in subnormal, and five in excess numbers of these cells. An additional 23 deficiencies blocked expression of the seam cell marker, in some cases without preventing cell proliferation. Two deficiencies result in multinucleate seam cells. Deficiencies were also identified that result in subnormal numbers of epidermal cells, hyperfusion of epidermal cells into a large syncytium, or aberrant epidermal differentiation. Finally, analysis of internal epithelia revealed deficiencies that cause defects in formation of internal organs, including circularization of the intestine and bifurcation of the pharynx lumen. This study reveals that many regions of the C. elegans genome are required zygotically for patterning of the epidermis and other epithelia.

scholarly journals Mutations Affecting Nerve Attachment of Caenorhabditis elegans

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1611-1622 ◽  
Author(s):  
Go Shioi ◽  
Michinari Shoji ◽  
Masashi Nakamura ◽  
Takeshi Ishihara ◽  
Isao Katsura ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Body Wall ◽  
The Body ◽  
Genetic Loci ◽  
Muscle Attachment ◽  
C Elegans ◽  
Ventral Cord ◽  
Excretory Canal

Abstract Using a pan-neuronal GFP marker, a morphological screen was performed to detect Caenorhabditis elegans larval lethal mutants with severely disorganized major nerve cords. We recovered and characterized 21 mutants that displayed displacement or detachment of the ventral nerve cord from the body wall (Ven: ventral cord abnormal). Six mutations defined three novel genetic loci: ven-1, ven-2, and ven-3. Fifteen mutations proved to be alleles of previously identified muscle attachment/positioning genes, mup-4, mua-1, mua-5, and mua-6. All the mutants also displayed muscle attachment/positioning defects characteristic of mua/mup mutants. The pan-neuronal GFP marker also revealed that mutants of other mua/mup loci, such as mup-1, mup-2, and mua-2, exhibited the Ven defect. The hypodermis, the excretory canal, and the gonad were morphologically abnormal in some of the mutants. The pleiotropic nature of the defects indicates that ven and mua/mup genes are required generally for the maintenance of attachment of tissues to the body wall in C. elegans.

scholarly journals Forces drive basement membrane invasion inCaenorhabditis elegans

2018 ◽  
Vol 115 (45) ◽  
pp. 11537-11542 ◽  
Author(s):  
Rodrigo Cáceres ◽  
Nagagireesh Bojanala ◽  
Laura C. Kelley ◽  
Jes Dreier ◽  
John Manzi ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Basement Membrane ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Force Production ◽  
Developmental Event ◽  
C Elegans ◽  
Anchor Cell

During invasion, cells breach basement membrane (BM) barriers with actin-rich protrusions. It remains unclear, however, whether actin polymerization applies pushing forces to help break through BM, or whether actin filaments play a passive role as scaffolding for targeting invasive machinery. Here, using the developmental event of anchor cell (AC) invasion inCaenorhabditis elegans, we observe that the AC deforms the BM and underlying tissue just before invasion, exerting forces in the tens of nanonewtons range. Deformation is driven by actin polymerization nucleated by the Arp2/3 complex and its activators, whereas formins and cross-linkers are dispensable. Delays in invasion upon actin regulator loss are not caused by defects in AC polarity, trafficking, or secretion, as appropriate markers are correctly localized in the AC even when actin is reduced and invasion is disrupted. Overall force production emerges from this study as one of the main tools that invading cells use to promote BM disruption inC. elegans.

scholarly journals The organisation and functions of local Ca2+ signals

2001 ◽  
Vol 114 (12) ◽  
pp. 2213-2222 ◽  
Author(s):  
Martin D. Bootman ◽  
Peter Lipp ◽  
Michael J. Berridge
Keyword(s):  
Cell Proliferation ◽  
Gene Transcription ◽  
Cell Biology ◽  
Building Blocks ◽  
Cell Types ◽  
Diverse Range ◽  
Cellular Processes ◽  
Different Cell Types ◽  
Intracellular Messenger ◽  
Sensory Mechanisms

Calcium (Ca2+) is a ubiquitous intracellular messenger, controlling a diverse range of cellular processes, such as gene transcription, muscle contraction and cell proliferation. The ability of a simple ion such as Ca2+ to play a pivotal role in cell biology results from the facility that cells have to shape Ca2+ signals in space, time and amplitude. To generate and interpret the variety of observed Ca2+ signals, different cell types employ components selected from a Ca2+ signalling ‘toolkit’, which comprises an array of homeostatic and sensory mechanisms. By mixing and matching components from the toolkit, cells can obtain Ca2+ signals that suit their physiology. Recent studies have demonstrated the importance of local Ca2+ signals in defining the specificity of the interaction of Ca2+ with its targets. Furthermore, local Ca2+ signals are the triggers and building blocks for larger global signals that propagate throughout cells.

scholarly journals Cryo-Electron Microscopy Structure and Interactions of the Human Cytomegalovirus gHgLgO Trimer with Platelet-Derived Growth Factor Receptor Alpha

mBio ◽  
2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Jing Liu ◽  
Adam Vanarsdall ◽  
Dong-Hua Chen ◽  
Andrea Chin ◽  
David Johnson ◽  
...  
Keyword(s):  
Birth Defects ◽  
Adult Population ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
The Body ◽  
Platelet Derived Growth Factor ◽  
Cryo Electron Microscopy ◽  
Factor Receptor Alpha ◽  
Complex Protein ◽  
Different Cell Types

HCMV is a herpesvirus that infects a large percentage of the adult population and causes significant levels of disease in immunocompromised individuals and birth defects in the developing fetus. The virus encodes a complex protein machinery that coordinates infection of different cell types in the body, including a trimer formed of gH, gL, and gO subunits.

scholarly journals Screening for Presenilin Inhibitors Using the Free-Living Nematode, Caenorhabditis elegans

2004 ◽  
Vol 9 (2) ◽  
pp. 147-152 ◽  
Author(s):  
Brenda R. Ellerbrock ◽  
Eileen M. Coscarelli ◽  
Mark E. Gurney ◽  
Timothy G. Geary
Keyword(s):  
Caenorhabditis Elegans ◽  
High Throughput Screening ◽  
Screening Method ◽  
Genetic System ◽  
Body Cavity ◽  
Egg Laying ◽  
The Body ◽  
Loss Of Function ◽  
C Elegans ◽  
Automated Method

Caenorhabditis elegans contains 3 homologs of presenilin genes that are associated with Alzheimer s disease. Loss-of-function mutations in C. elegans genes cause a defect in egg laying. In humans, loss of presenilin-1 (PS1) function reduces amyloid-beta peptide processing from the amyloid protein precursor. Worms were screened for compounds that block egg laying, phenocopying presenilin loss of function. To accommodate even relatively high throughput screening, a semi-automated method to quantify egg laying was devised by measuring the chitinase released into the culture medium. Chitinase is released by hatching eggs, but little is shed into the medium from the body cavity of a hermaphrodite with an egg laying deficient ( egl) phenotype. Assay validation involved measuring chitinase release from wild-type C. elegans (N2 strain), sel-12 presenilin loss-of-function mutants, and 2 strains of C. elegans with mutations in the egl-36K+ channel gene. Failure to find specific presenilin inhibitors in this collection likely reflects the small number of compounds tested, rather than a flaw in screening strategy. Absent defined biochemical pathways for presenilin, this screening method, which takes advantage of the genetic system available in C. elegans and its historical use for anthelminthic screening, permits an entry into mechanism-based discovery of drugs for Alzheimer s disease. ( Journal of Biomolecular Screening 2004:147-152)

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