Notochord morphogenesis in Xenopus laevis: simulation of cell behavior underlying tissue convergence and extension

Development ◽  
1991 ◽  
Vol 113 (4) ◽  
pp. 1231-1244 ◽  
Author(s):  
M. Weliky ◽  
S. Minsuk ◽  
R. Keller ◽  
G. Oster
Keyword(s):  
Xenopus Laevis ◽  
Cell Motility ◽  
Cell Polarization ◽  
Contact Inhibition ◽  
Cell Behavior ◽  
Directional Bias ◽  
Cell Movements ◽  
Cell Behaviors ◽  
Geometric Conditions

Cell intercalation and cell shape changes drive notochord morphogenesis in the African frog, Xenopus laevis. Experimental observations show that cells elongate mediolaterally and intercalate between one another, causing the notochord to lengthen and narrow. Descriptive observations provide few clues as to the mechanisms that coordinate and drive these cell movements. It is possible that a few rules governing cell behavior could orchestrate the shaping of the entire tissue. We test this hypothesis by constructing a computer model of the tissue to investigate how rules governing cell motility and cell-cell interactions can account for the major features of notochord morphogenesis. These rules are drawn from the literature on in vitro cell studies and experimental observations of notochord cell behavior. The following types of motility rules are investigated: (1) refractory tissue boundaries that inhibit cell motility, (2) statistical persistence of motion, (3) contact inhibition of protrusion between cells, and (4) polarized and nonpolarized protrusive activity. We show that only the combination of refractory boundaries, contact inhibition and polarized protrusive activity reproduces normal notochord development. Guided by these rules, cells spontaneously align into a parallel array of elongating cells. Self alignment optimizes the geometric conditions for polarized protrusive activity by progressively minimizing contact inhibition between cells. Cell polarization, initiated at refractory tissue boundaries, spreads along successive cell rows into the tissue interior as cells restrict and constrain their neighbors' directional bias. The model demonstrates that several experimentally observed intrinsic cell behaviors, operating simultaneously, may underlie the generation of coordinated cell movements within the developing notochord.

scholarly journals Twinfilin1 controls lamellipodial protrusive activity and actin turnover during vertebrate gastrulation

2020 ◽  
Author(s):  
Caitlin C. Devitt ◽  
Chanjae Lee ◽  
Rachael M. Cox ◽  
Ophelia Papoulas ◽  
José Alvarado ◽  
...  
Keyword(s):  
Animal Cell ◽  
Dynamic Control ◽  
Deep Understanding ◽  
Early Embryo ◽  
Cell Polarization ◽  
Actin Dynamics ◽  
Convergent Extension ◽  
Cell Movements ◽  
Actin Turnover

AbstractThe dynamic control of the actin cytoskeleton is a key aspect of essentially all animal cell movements. Experiments in single migrating cells and in vitro systems have provided an exceptionally deep understanding of actin dynamics. However, we still know relatively little of how these systems are tuned in cell-type specific ways, for example in the context of collective cell movements that sculpt the early embryo. Here, we provide an analysis of the actin severing and depolymerization machinery during vertebrate gastrulation, with a focus on Twinfilin1. We confirm previous results on the role of Twf1 in lamellipodia and extend those findings by linking Twf1, actin turnover, and cell polarization required for convergent extension during vertebrate gastrulation.

scholarly journals Virtual-tissue computer simulations define the roles of cell adhesion and proliferation in the onset of kidney cystic disease

2016 ◽  
Vol 27 (22) ◽  
pp. 3673-3685 ◽  
Author(s):  
Julio M. Belmonte ◽  
Sherry G. Clendenon ◽  
Guilherme M. Oliveira ◽  
Maciej H. Swat ◽  
Evan V. Greene ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Full Range ◽  
Contact Inhibition ◽  
Inhibition Of Proliferation ◽  
Cell Behaviors ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cell Adhesion And Proliferation ◽  
Cell Cell

In autosomal dominant polycystic kidney disease (ADPKD), cysts accumulate and progressively impair renal function. Mutations in PKD1 and PKD2 genes are causally linked to ADPKD, but how these mutations drive cell behaviors that underlie ADPKD pathogenesis is unknown. Human ADPKD cysts frequently express cadherin-8 (cad8), and expression of cad8 ectopically in vitro suffices to initiate cystogenesis. To explore cell behavioral mechanisms of cad8-driven cyst initiation, we developed a virtual-tissue computer model. Our simulations predicted that either reduced cell–cell adhesion or reduced contact inhibition of proliferation triggers cyst induction. To reproduce the full range of cyst morphologies observed in vivo, changes in both cell adhesion and proliferation are required. However, only loss-of-adhesion simulations produced morphologies matching in vitro cad8-induced cysts. Conversely, the saccular cysts described by others arise predominantly by decreased contact inhibition, that is, increased proliferation. In vitro experiments confirmed that cell–cell adhesion was reduced and proliferation was increased by ectopic cad8 expression. We conclude that adhesion loss due to cadherin type switching in ADPKD suffices to drive cystogenesis. Thus, control of cadherin type switching provides a new target for therapeutic intervention.

Induction of notochord cell intercalation behavior and differentiation by progressive signals in the gastrula of Xenopus laevis

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3311-3321 ◽  
Author(s):  
C. Domingo ◽  
R. Keller
Keyword(s):  
Xenopus Laevis ◽  
Behavioral Changes ◽  
Cell Behavior ◽  
Convergent Extension ◽  
Notochordal Cell ◽  
Cell Behaviors ◽  
Notochord Cell ◽  
Light Fluorescence ◽  
Cell Intercalation ◽  
Somitic Mesoderm

We show that notochord-inducing signals are present during Xenopus laevis gastrulation and that they are important for both inducing and organizing cell behavior and differentiation in the notochord. Previous work showed that convergent extension of prospective notochordal and somitic mesoderm occurs by mediolateral cell intercalation to produce a longer, narrower tissue. Mediolateral cell intercalation is driven by bipolar, mediolaterally directed protrusive activity that elongates cells and then pulls them between one another along the mediolateral axis. This cell behavior, and subsequent notochordal cell differentiation, begins anteriorly and spreads posteriorly along the notochordal-somitic boundary, and from this lateral boundary progresses medially towards the center of the notochord field. To examine whether these progressions of cell behaviors and differentiation are induced and organized during gastrulation, we grafted labeled cells from the prospective notochordal, somitic and epidermal regions of the gastrula into the notochordal region and monitored their behavior by low light, fluorescence videomicroscopy. Prospective notochordal, epidermal and somitic cells expressed mediolateral cell intercalation behavior in an anterior-to-posterior and lateral-to-medial order established by the host notochord. Behavioral changes were induced first and most dramatically among cells grafted next to the notochordal-somitic boundary, particularly those in direct contact with the boundary, suggesting that the boundary may provide signals that both induce and organize notochordal cell behaviors. By physically impeding normal convergent extension movements, notochordal cell behaviors and differentiation were restricted to the anteriormost notochordal region and to the lateral notochordal-somitic boundary. These results show that mediolateral cell intercalation behavior and notochordal differentiation can be induced in the gastrula stage, among cells not normally expressing these characteristics, and that these characteristics are induced progressively, most likely by signals emanating from the notochordal-somitic boundary. In addition, they show that morphogenetic movements during gastrulation are necessary for complete notochord formation and that the prospective notochord region is not determined by the onset of gastrulation.

scholarly journals In vitro cell behavior of osteoblasts on Pyrost bone substitute

1997 ◽  
Vol 247 (2) ◽  
pp. 164-169 ◽  
Author(s):  
Yang-Hwei Tsuang ◽  
Feng-Huei Lin ◽  
Jui-Sheng Sun ◽  
Yi-Shiong Hang ◽  
Hwa-Chang Liu
Keyword(s):  
Bone Substitute ◽  
Cell Behavior

scholarly journals Role of the V1G1 subunit of V-ATPase in breast cancer cell migration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria De Luca ◽  
Roberta Romano ◽  
Cecilia Bucci
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Motility ◽  
Cancer Progression ◽  
Tumor Formation ◽  
Downstream Signaling ◽  
Late Endosomes ◽  
Intracellular Compartments

AbstractV-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.

scholarly journals Involvement of single-stranded tails in homologous recombination of DNA injected into Xenopus laevis oocyte nuclei.

1991 ◽  
Vol 11 (6) ◽  
pp. 3268-3277 ◽  
Author(s):  
E Maryon ◽  
D Carroll
Keyword(s):  
Homologous Recombination ◽  
Xenopus Laevis ◽  
Gel Electrophoresis ◽  
Xenopus Laevis Oocyte ◽  
Molecular Models ◽  
Mixed Substrates ◽  
Two Dimensional Gel Electrophoresis ◽  
Recombination Pathway ◽  
Made In

Homologous recombination of DNA molecules injected into Xenopus laevis oocyte nuclei is extremely efficient when those molecules are linear and have overlapping homologous ends. It was previously shown that a 5'----3' exonuclease activity in oocytes attacks injected linear DNAs and leaves them with single-stranded 3' tails. We tested the hypothesis that such tailed molecules are early intermediates on the pathway to recombination products. Substrates with 3' tails were made in vitro and injected into oocytes, where they recombined rapidly and efficiently. In experiments with mixed substrates, molecules with 3' tails entered recombination intermediates and products more rapidly than did molecules with flush ends. Molecules endowed in vitro with 5' tails also recombined efficiently in oocytes, but their rate was not faster than for flush-ended substrates. In most cases, the 5' tails served as templates for resynthesis of the 3' strands, regenerating duplex ends which then entered the normal recombination pathway. In oocytes from one animal, some of the 5' tails were removed, and this was exacerbated when resynthesis was partially blocked. Analysis by two-dimensional gel electrophoresis of recombination intermediates from 5'-tailed substrates confirmed that they had acquired 3' tails as a result of the action of the 5'----3' exonuclease. These results demonstrate that homologous recombination in oocytes proceeds via a pathway that involves single-stranded 3' tails. Molecular models incorporating this feature are discussed.

Regulation of Osteoblast-Like Cell Behaviors on Hydroxyapatite by Electrical Polarization

2007 ◽  
Vol 361-363 ◽  
pp. 1055-1058 ◽  
Author(s):  
Miho Nakamura ◽  
Akiko Nagai ◽  
Natalie Ohashi ◽  
Yumi Tanaka ◽  
Yasutaka Sekijima ◽  
...  
Keyword(s):  
Cell Movement ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Wound Healing Assay ◽  
Cell Behaviors ◽  
Stress Fiber Formation ◽  
Cytoskeleton Reorganization ◽  
Osteoblast Adhesion ◽  
As Stress

The osteoblast adhesion to the substrates are recognized to play a fundamental role in osteoconduction process. The purpose of this study was to evaluate the in vitro behavior of osteoblasts cultured on polarized hydroxyapatite (HA), having the enhanced osteobonding abilities. Osteoblast-like cells were seeded onto the polarized HA and investigated the adhesion and motility. The polarization had no effects on the percentage of the number of the spreaded cells against all the adhered cells, but had significant effects on the elongation of adhered cells from fluorescent observation and on the cell motility showed by the wound healing assay. The charges induced on the HA surface accelerated the cytoskeleton reorganization of the adhered cells cultured on HA specimens. The acceleration was emerged as the cells shape, actin filament pattern such as stress fiber formation, and the prolongation of the cell movement distances.

scholarly journals Inositol incorporation into phosphoinositides in retinal horizontal cells of Xenopus laevis: enhancement by acetylcholine, inhibition by glycine.

1984 ◽  
Vol 99 (2) ◽  
pp. 686-691 ◽  
Author(s):  
R E Anderson ◽  
J G Hollyfield
Keyword(s):  
Xenopus Laevis ◽  
Culture Medium ◽  
Photoreceptor Cells ◽  
Horizontal Cells ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Light Effect ◽  
Synaptic Inputs ◽  
Absorption Of Light

The absorption of light by photoreceptor cells leads to an increased incorporation of [2-3H]inositol into phosphoinositides of horizontal cells in the retina of Xenopus laevis in vitro. We have identified several retinal neurotransmitters that are involved in regulating this response. Incubation with glycine, the neurotransmitter of an interplexiform cell that has direct synaptic input onto horizontal cells, abolishes the light effect. This inhibition is reversed by preincubation with strychnine. Acetylcholine added to the culture medium enhances the incorporation of [2-3H]inositol into phosphoinositides in horizontal cells when retinas are incubated in the dark. This effect is inhibited by preincubation with atropine. However, atropine alone does not inhibit the light-enhanced incorporation of [2-3H]inositol into phosphoinositides in the retina. gamma-Aminobutyric acid, the neurotransmitter of retinal horizontal cells in X. laevis, as well as dopamine and norepinephrine, have no effect on the incorporation of [2-3H]inositol into phosphoinositides. These studies demonstrate that the light-enhanced incorporation of [2-3H]inositol into phosphoinositides of retinal horizontal cells is regulated by specific neurotransmitters, and that there are probably several synaptic inputs into horizontal cells which control this process.

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