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 Twinfilin1 controls lamellipodial protrusive activity and actin turnover during vertebrate gastrulation

2021 ◽  
Author(s):  
Caitlin C. Devitt ◽  
Chanjae Lee ◽  
Rachael M. Cox ◽  
Ophelia Papoulas ◽  
José Alvarado ◽  
...  
Keyword(s):  
Animal Cell ◽  
Dynamic Control ◽  
Deep Understanding ◽  
Early Embryo ◽  
Actin Dynamics ◽  
Convergent Extension ◽  
Cell Movements ◽  
Actin Cables

The 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 (Twf1). We find that Twf1 is essential for convergent extension, and loss of Twf1 results in a failure of lamellipodial dynamics and polarity. Moreover, Twf1 loss results in a failure to assemble polarized cytoplasmic actin cables essential for convergent extension. These data provide an in vivo complement to our more-extensive understanding of Twf1 action in vitro and provide new links between the core machinery of actin regulation and specialized cell behaviors of embryonic morphogenesis.

scholarly journals Wnt5b integrates Fak1a to mediate gastrulation cell movements via Rac1 and Cdc42

Open Biology ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 190273
Author(s):  
I-Chen Hung ◽  
Tsung-Ming Chen ◽  
Jing-Ping Lin ◽  
Yu-Ling Tai ◽  
Tang-Long Shen ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Early Embryogenesis ◽  
Actin Dynamics ◽  
Convergent Extension ◽  
Cortical Actin ◽  
Functional Interaction ◽  
Cell Movements ◽  
Cellular Pathways ◽  
Antisense Morpholino ◽  
Subthreshold Level

Focal adhesion kinase (FAK) mediates vital cellular pathways during development. Despite its necessity, how FAK regulates and integrates with other signals during early embryogenesis remains poorly understood. We found that the loss of Fak1a impaired epiboly, convergent extension and hypoblast cell migration in zebrafish embryos. We also observed a clear disturbance in cortical actin at the blastoderm margin and distribution of yolk syncytial nuclei. In addition, we investigated a possible link between Fak1a and a well-known gastrulation regulator, Wnt5b, and revealed that the overexpression of fak1a or wnt5b could cross-rescue convergence defects induced by a wnt5b or fak1a antisense morpholino (MO), respectively. Wnt5b and Fak1a were shown to converge in regulating Rac1 and Cdc42, which could synergistically rescue wnt5b and fak1a morphant phenotypes. Furthermore, we generated several alleles of fak1a mutants using CRISPR/Cas9, but those mutants only revealed mild gastrulation defects. However, injection of a subthreshold level of the wnt5b MO induced severe gastrulation defects in fak1a mutants, which suggested that the upregulated expression of wnt5b might complement the loss of Fak1a. Collectively, we demonstrated that a functional interaction between Wnt and FAK signalling mediates gastrulation cell movements via the possible regulation of Rac1 and Cdc42 and subsequent actin dynamics.

scholarly journals Furry is required for cell movements during gastrulation and functionally interacts with NDR1

2020 ◽  
Author(s):  
Ailen S. Cervino ◽  
Bruno Moretti ◽  
Carsten Stuckenholz ◽  
Hernán E. Grecco ◽  
Lance A. Davidson ◽  
...  
Keyword(s):  
Asymmetric Cell Division ◽  
Cell Polarization ◽  
Convergent Extension ◽  
Cellular Functions ◽  
Embryonic Axes ◽  
Cell Movements ◽  
Evolutionarily Conserved ◽  
Axis Elongation ◽  
Established Cell ◽  
Division Cell

AbstractGastrulation is a key event in animal embryogenesis during which the germ layers precursors are rearranged and the embryonic axes are established. Cell polarization is essential during gastrulation driving asymmetric cell division, cell movements and cell shape changes. Furry (Fry) gene encodes an evolutionarily conserved protein with a wide variety of cellular functions mostly related to cell polarization and morphogenesis in invertebrates. However, little is known about its function in vertebrate development. Here we show that in Xenopus, Fry participates in the regulation of morphogenetic processes during gastrulation. Using morpholino knock-down, we demonstrate a role of Fry in blastopore closure and dorsal axis elongation. Loss of Fry function drastically affects the movement and morphological polarization of cells during gastrulation, in addition to dorsal mesoderm convergent extension, responsible for head-to-tail elongation. Finally, we demonstrate a functional interaction between Fry and NDR1 kinase, providing evidence of an evolutionarily conserved complex required for morphogenesis.

scholarly journals Par-3 mediates the inhibition of LIM kinase 2 to regulate cofilin phosphorylation and tight junction assembly

2006 ◽  
Vol 172 (5) ◽  
pp. 671-678 ◽  
Author(s):  
Xinyu Chen ◽  
Ian G. Macara
Keyword(s):  
Tight Junction ◽  
Cell Polarization ◽  
Actin Dynamics ◽  
Lim Kinase ◽  
Kinase C ◽  
Cofilin Phosphorylation ◽  
Upstream Kinase ◽  
Novel Target ◽  
Axon Specification

The polarity protein Par-3 plays critical roles in axon specification and the establishment of epithelial apico-basal polarity. Par-3 associates with Par-6 and atypical protein kinase C and is required for the proper assembly of tight junctions, but the molecular basis for its functions is poorly understood. We now report that depletion of Par-3 elevates the phosphorylated pool of cofilin, a key regulator of actin dynamics. Expression of a nonphosphorylatable mutant of cofilin partially rescues tight junction assembly in cells lacking Par-3, as does the depletion of LIM kinase 2 (LIMK2), an upstream kinase for cofilin. Par-3 binds to LIMK2 but not to the related kinase LIMK1. Par-3 inhibits LIMK2 activity in vitro, and overexpressed Par-3 suppresses cofilin phosphorylation that is induced by lysophosphatidic acid. Our findings identify LIMK2 as a novel target of Par-3 and uncover a molecular mechanism by which Par-3 could regulate actin dynamics during cell polarization.

scholarly journals PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin–actin interactions

2015 ◽  
Vol 210 (5) ◽  
pp. 753-769 ◽  
Author(s):  
Nan Hyung Hong ◽  
Aidong Qi ◽  
Alissa M. Weaver
Keyword(s):  
Membrane Trafficking ◽  
Membrane Curvature ◽  
Actin Dynamics ◽  
Complex Activity ◽  
Actin Networks ◽  
Binding Partner ◽  
Late Endosomes ◽  
Actin Turnover ◽  
Direct Binding

Branched actin critically contributes to membrane trafficking by regulating membrane curvature, dynamics, fission, and transport. However, how actin dynamics are controlled at membranes is poorly understood. Here, we identify the branched actin regulator cortactin as a direct binding partner of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) and demonstrate that their interaction promotes turnover of late endosomal actin. In vitro biochemical studies indicated that cortactin binds PI(3,5)P2 via its actin filament-binding region. Furthermore, PI(3,5)P2 competed with actin filaments for binding to cortactin, thereby antagonizing cortactin activity. These findings suggest that PI(3,5)P2 formation on endosomes may remove cortactin from endosome-associated branched actin. Indeed, inhibition of PI(3,5)P2 production led to cortactin accumulation and actin stabilization on Rab7+ endosomes. Conversely, inhibition of Arp2/3 complex activity greatly reduced cortactin localization to late endosomes. Knockdown of cortactin reversed PI(3,5)P2-inhibitor–induced actin accumulation and stabilization on endosomes. These data suggest a model in which PI(3,5)P2 binding removes cortactin from late endosomal branched actin networks and thereby promotes net actin turnover.

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 Furry is required for cell movements during gastrulation and functionally interacts with NDR1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ailen S. Cervino ◽  
Bruno Moretti ◽  
Carsten Stuckenholz ◽  
Hernán E. Grecco ◽  
Lance A. Davidson ◽  
...  
Keyword(s):  
Asymmetric Cell Division ◽  
Cell Polarization ◽  
Convergent Extension ◽  
Cellular Functions ◽  
Embryonic Axes ◽  
Cell Movements ◽  
Evolutionarily Conserved ◽  
Dorsal Mesoderm ◽  
Axis Elongation ◽  
Division Cell

AbstractGastrulation is a key event in animal embryogenesis during which germ layer precursors are rearranged and the embryonic axes are established. Cell polarization is essential during gastrulation, driving asymmetric cell division, cell movements, and cell shape changes. Thefurry(fry) gene encodes an evolutionarily conserved protein with a wide variety of cellular functions, including cell polarization and morphogenesis in invertebrates. However, little is known about its function in vertebrate development. Here, we show that inXenopus,Fry plays a role in morphogenetic processes during gastrulation, in addition to its previously described function in the regulation of dorsal mesoderm gene expression. Using morpholino knock-down, we demonstrate a distinct role for Fry in blastopore closure and dorsal axis elongation. Loss of Fry function drastically affects the movement and morphological polarization of cells during gastrulation and disrupts dorsal mesoderm convergent extension, responsible for head-to-tail elongation. Finally, we evaluate a functional interaction between Fry and NDR1 kinase, providing evidence of an evolutionarily conserved complex required for morphogenesis.

scholarly journals The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zhang ◽  
Zhaohui Zhong ◽  
Mei Li ◽  
Jingyi Chen ◽  
Tingru Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
The Cancer Genome Atlas ◽  
Actin Dynamics ◽  
Elevated Expression ◽  
Sw480 Cells ◽  
And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

An Animal Protection Sponsor's View of MEIC

1997 ◽  
Vol 25 (3) ◽  
pp. 343-345
Author(s):  
Ethel Thurston
Keyword(s):  
Gold Standard ◽  
Animal Cell ◽  
Scientific Evidence ◽  
In Vitro Cytotoxicity ◽  
In Vitro Tests ◽  
Blood Concentrations ◽  
Animal Protection ◽  
Animal Tests ◽  
Lethal Blood

The Multicenter Evaluation of In Vitro Cytotoxicity programme is most important to animal protection, since it has validated 64 in vitro tests using advanced human data for 50 chemicals as the “gold standard”. Therefore, it has been able to compare animal cell tests, human cell tests and whole-animal tests fairly with unbiased scientific evidence. Added bonuses have included the identification and development of missing in vitro information (“missing tests”), publication of time-related lethal blood concentrations for all 50 chemicals, and some preliminary plans to resolve the 50,000 untested (or poorly tested) chemicals in the chemical mountain.

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