scholarly journals Rho1 activation recapitulates early gastrulation events in the ventral, but not dorsal, epithelium of Drosophila embryos

2020 ◽  
Author(s):  
Ashley Rich ◽  
Richard G. Fehon ◽  
Michael Glotzer
Keyword(s):  
Tissue Level ◽  
Tissue Morphogenesis ◽  
Apical Constriction ◽  
Cell Movements ◽  
Highly Active ◽  
Ventral Furrow ◽  
Morphogenetic Event ◽  
Specific Factors ◽  
Dorsal Cells ◽  
Drosophila Embryos

AbstractVentral furrow formation, the first step in Drosophila gastrulation, is a well-studied example of tissue morphogenesis. Rho1 is highly active in a subset of ventral cells and is required for this morphogenetic event. However, it is unclear whether spatially patterned Rho1 activity alone is sufficient to recapitulate all aspects of this morphogenetic event, including anisotropic apical constriction and coordinated cell movements. Here, using an optogenetic probe that rapidly and robustly activates Rho1 in Drosophila tissues, we show that Rho1 activity induces ectopic deformations in the dorsal and ventral epithelia of Drosophila embryos. These perturbations reveal substantial differences in how ventral and dorsal cells, both within and outside the zone of Rho1 activation, respond to spatially and temporally identical patterns of Rho1 activation. Our results demonstrate that an asymmetric zone of Rho1 activity is not sufficient to recapitulate ventral furrow formation and indicate that additional, ventral-specific factors contribute to the cell- and tissue-level behaviors that emerge during ventral furrow formation.

scholarly journals Rho1 activation recapitulates early gastrulation events in the ventral, but not dorsal, epithelium of Drosophila embryos

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ashley Rich ◽  
Richard G Fehon ◽  
Michael Glotzer
Keyword(s):  
Tissue Level ◽  
Tissue Morphogenesis ◽  
Apical Constriction ◽  
Cell Movements ◽  
Highly Active ◽  
Ventral Furrow ◽  
Morphogenetic Event ◽  
Specific Factors ◽  
Dorsal Cells ◽  
Drosophila Embryos

Ventral furrow formation, the first step in Drosophila gastrulation, is a well-studied example of tissue morphogenesis. Rho1 is highly active in a subset of ventral cells and is required for this morphogenetic event. However, it is unclear whether spatially patterned Rho1 activity alone is sufficient to recapitulate all aspects of this morphogenetic event, including anisotropic apical constriction and coordinated cell movements. Here, using an optogenetic probe that rapidly and robustly activates Rho1 in Drosophila tissues, we show that Rho1 activity induces ectopic deformations in the dorsal and ventral epithelia of Drosophila embryos. These perturbations reveal substantial differences in how ventral and dorsal cells, both within and outside the zone of Rho1 activation, respond to spatially and temporally identical patterns of Rho1 activation. Our results demonstrate that an asymmetric zone of Rho1 activity is not sufficient to recapitulate ventral furrow formation and reveal that additional, ventral-specific factors contribute to the cell- and tissue-level behaviors that emerge during ventral furrow formation.

scholarly journals Apical Constriction Reversal upon Mitotic Entry Underlies Different Morphogenetic Outcomes of Cell Division

2020 ◽  
Vol 31 (16) ◽  
pp. 1663-1674 ◽  
Author(s):  
Clint S. Ko ◽  
Prateek Kalakuntla ◽  
Adam C. Martin
Keyword(s):  
Cell Division ◽  
Tissue Level ◽  
Spatiotemporal Patterns ◽  
Force Generation ◽  
Tissue Morphogenesis ◽  
Apical Constriction ◽  
Mitotic Entry ◽  
Cell Divisions

Cell divisions can either promote or inhibit tissue morphogenesis. In contractile epithelia, mitotic entry disrupts medioapical myosin activation and reverses apical constriction. We found that different spatiotemporal patterns of mitotic entry and the resultant changes in force generation at the tissue level dictate distinct tissue shape outcomes.

scholarly journals Computational modelling unveils how epiblast remodelling and positioning rely on trophectoderm morphogenesis during mouse implantation

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254763
Author(s):  
Joel Dokmegang ◽  
Moi Hoon Yap ◽  
Liangxiu Han ◽  
Matteo Cavaliere ◽  
René Doursat
Keyword(s):  
Computational Modelling ◽  
Tissue Level ◽  
Apical Surface ◽  
Mammalian Embryo ◽  
Agent Based ◽  
Mechanical Constraints ◽  
Morphogenetic Event ◽  
Theoretical Evidence ◽  
Experimental Findings ◽  
Modelling Methods

Understanding the processes by which the mammalian embryo implants in the maternal uterus is a long-standing challenge in embryology. New insights into this morphogenetic event could be of great importance in helping, for example, to reduce human infertility. During implantation the blastocyst, composed of epiblast, trophectoderm and primitive endoderm, undergoes significant remodelling from an oval ball to an egg cylinder. A main feature of this transformation is symmetry breaking and reshaping of the epiblast into a “cup”. Based on previous studies, we hypothesise that this event is the result of mechanical constraints originating from the trophectoderm, which is also significantly transformed during this process. In order to investigate this hypothesis we propose MG# (MechanoGenetic Sharp), an original computational model of biomechanics able to reproduce key cell shape changes and tissue level behaviours in silico. With this model, we simulate epiblast and trophectoderm morphogenesis during implantation. First, our results uphold experimental findings that repulsion at the apical surface of the epiblast is essential to drive lumenogenesis. Then, we provide new theoretical evidence that trophectoderm morphogenesis indeed can dictate the cup shape of the epiblast and fosters its movement towards the uterine tissue. Our results offer novel mechanical insights into mouse peri-implantation and highlight the usefulness of agent-based modelling methods in the study of embryogenesis.

scholarly journals Neuralized regulates a travelling wave of Epithelium-to-Neural Stem Cell morphogenesis in Drosophila

2020 ◽  
Author(s):  
Chloé Shard ◽  
Juan Luna-Escalante ◽  
François Schweisguth
Keyword(s):  
Stem Cells ◽  
Ubiquitin Ligase ◽  
Epithelial To Mesenchymal Transition ◽  
Optic Lobe ◽  
E3 Ubiquitin Ligase ◽  
Tissue Level ◽  
Travelling Wave ◽  
Cell Morphogenesis ◽  
Apical Constriction ◽  
Mesenchymal Transition

AbstractMany tissues are produced during development by specialized progenitor cells emanating from epithelia via an Epithelial-to-Mesenchymal Transition (EMT). Most studies have so far focused on cases involving single or isolated groups of cells. Here we describe an EMT-like process that requires tissue level coordination. This EMT-like process occurs along a continuous front in the Drosophila optic lobe neuroepithelium to produce neural stem cells (NSCs). We find that emerging NSCs remain epithelial and apically constrict before dividing asymmetrically to produce neurons. Apical constriction is associated with contractile myosin pulses and requires the E3 ubiquitin ligase Neuralized and RhoGEF3. Neuralized down-regulates the apical protein Crumbs via its interaction with Stardust. Disrupting the regulation of Crumbs by Neuralized led to defects in apical constriction and junctional myosin accumulation, and to imprecision in the integration of emerging NSCs into the transition front. Neuralized therefore appears to mechanically couple NSC fate acquisition with cell-cell rearrangement to promote smooth progression of the differentiation front.

scholarly journals A Nodal/Eph signalling relay drives the transition from apical constriction to apico-basal shortening in ascidian endoderm invagination

Development ◽  
2020 ◽  
Vol 147 (15) ◽  
pp. dev186965
Author(s):  
Ulla-Maj Fiuza ◽  
Takefumi Negishi ◽  
Alice Rouan ◽  
Hitoyoshi Yasuo ◽  
Patrick Lemaire
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Ciona Intestinalis ◽  
Precursor Cells ◽  
Endodermal Cell ◽  
Apical Constriction ◽  
Fate Specification ◽  
Endoderm Cell ◽  
Ascidian Species ◽  
Morphogenetic Event

ABSTRACTGastrulation is the first major morphogenetic event during animal embryogenesis. Ascidian gastrulation starts with the invagination of 10 endodermal precursor cells between the 64- and late 112-cell stages. This process occurs in the absence of endodermal cell division and in two steps, driven by myosin-dependent contractions of the acto-myosin network. First, endoderm precursors constrict their apex. Second, they shorten apico-basally, while retaining small apical surfaces, thereby causing invagination. The mechanisms that prevent endoderm cell division, trigger the transition between step 1 and step 2, and drive apico-basal shortening have remained elusive. Here, we demonstrate a conserved role for Nodal and Eph signalling during invagination in two distantly related ascidian species, Phallusia mammillata and Ciona intestinalis. Specifically, we show that the transition to step 2 is triggered by Nodal relayed by Eph signalling. In addition, our results indicate that Eph signalling lengthens the endodermal cell cycle, independently of Nodal. Finally, we find that both Nodal and Eph signals are dispensable for endoderm fate specification. These results illustrate commonalities as well as differences in the action of Nodal during ascidian and vertebrate gastrulation.

scholarly journals Actin and myosin dynamics are independent during Drosophila embryonic wound repair

2019 ◽  
Vol 30 (23) ◽  
pp. 2901-2912
Author(s):  
Anna B. Kobb ◽  
Katheryn E. Rothenberg ◽  
Rodrigo Fernandez-Gonzalez
Keyword(s):  
Wound Repair ◽  
Wound Closure ◽  
Molecular Motor ◽  
Wound Edge ◽  
Cell Movements ◽  
Nonmuscle Myosin Ii ◽  
Wound Margin ◽  
Wound Healing Response ◽  
Disease Cell ◽  
Drosophila Embryos

Collective cell movements play a central role in embryonic development, tissue repair, and metastatic disease. Cell movements are often coordinated by supracellular networks formed by the cytoskeletal protein actin and the molecular motor nonmuscle myosin II. During wound closure in the embryonic epidermis, the cells around the wound migrate collectively into the damaged region. In Drosophila embryos, mechanical tension stabilizes myosin at the wound edge, facilitating the assembly of a supracellular myosin cable around the wound that coordinates cell migration. Here, we show that actin is also stabilized at the wound edge. However, loss of tension or myosin activity does not affect the dynamics of actin at the wound margin. Conversely, pharmacological stabilization of actin does not affect myosin levels or dynamics around the wound. Together, our data suggest that actin and myosin are independently regulated during embryonic wound closure, thus conferring robustness to the embryonic wound healing response.

scholarly journals Integration of contractile forces during tissue invagination

2010 ◽  
Vol 188 (5) ◽  
pp. 735-749 ◽  
Author(s):  
Adam C. Martin ◽  
Michael Gelbart ◽  
Rodrigo Fernandez-Gonzalez ◽  
Matthias Kaschube ◽  
Eric F. Wieschaus
Keyword(s):  
Cell Shape ◽  
Control Cell ◽  
Adherens Junction ◽  
Tissue Level ◽  
Epithelial Morphogenesis ◽  
Apical Constriction ◽  
Contractile Forces ◽  
Actomyosin Cytoskeleton ◽  
Cellular Forces ◽  
Anterior Posterior

Contractile forces generated by the actomyosin cytoskeleton within individual cells collectively generate tissue-level force during epithelial morphogenesis. During Drosophila mesoderm invagination, pulsed actomyosin meshwork contractions and a ratchet-like stabilization of cell shape drive apical constriction. Here, we investigate how contractile forces are integrated across the tissue. Reducing adherens junction (AJ) levels or ablating actomyosin meshworks causes tissue-wide epithelial tears, which release tension that is predominantly oriented along the anterior–posterior (a-p) embryonic axis. Epithelial tears allow cells normally elongated along the a-p axis to constrict isotropically, which suggests that apical constriction generates anisotropic epithelial tension that feeds back to control cell shape. Epithelial tension requires the transcription factor Twist, which stabilizes apical myosin II, promoting the formation of a supracellular actomyosin meshwork in which radial actomyosin fibers are joined end-to-end at spot AJs. Thus, pulsed actomyosin contractions require a supracellular, tensile meshwork to transmit cellular forces to the tissue level during morphogenesis.

scholarly journals Viral Blip Dynamics during Highly Active Antiretroviral Therapy

2003 ◽  
Vol 77 (22) ◽  
pp. 12165-12172 ◽  
Author(s):  
Michele Di Mascio ◽  
Martin Markowitz ◽  
Michael Louie ◽  
Christine Hogan ◽  
Arlene Hurley ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Extended Period ◽  
Two Phase ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Specific Factors ◽  
The Mean ◽  
Hiv 1

ABSTRACT Although intermittent episodes of low-level viremia are often observed in well-suppressed highly active antiretroviral therapy (HAART)-treated patients, the timing and amplitude of viral blips have never been examined in detail. We analyze here the dynamics of viral blips, i.e., plasma VL measurements of >50 copies/ml, in 123 HAART-treated patients monitored for a mean of 2.6 years (range, 5 months to 5.3 years). The mean (± the standard deviation) blip frequency was 0.09 ± 0.11/sample, with about one-third of patients showing no viral blips. The mean viral blip amplitude was 158 ± 132 human immunodeficiency virus type 1 (HIV-1) RNA copies/ml. Analysis of the blip frequency and amplitude distributions suggest that two blips less than 22 days apart have a significant chance of being part of the same episode of viremia. The data are consistent with a hypothetical model in which each episode of viremia consists of a phase of VL rise, followed by two-phase exponential decay. Thus, the term “viral blip” may be a misnomer, since viral replication appears to be occurring over an extended period. Neither the frequency nor the amplitude of viral blips increases with longer periods of observation, but the frequency is inversely correlated with the CD4+-T-cell count at the start of therapy, suggesting that host-specific factors but not treatment fatigue are determinants of blip frequency.

scholarly journals Loss of Gα12/13 exacerbates apical area dependence of actomyosin contractility

2016 ◽  
Vol 27 (22) ◽  
pp. 3526-3536 ◽  
Author(s):  
Shicong Xie ◽  
Frank M. Mason ◽  
Adam C. Martin
Keyword(s):  
Cell Shape ◽  
Rho Kinase ◽  
Dependent Manner ◽  
Timely Initiation ◽  
Apical Constriction ◽  
Size Dependent ◽  
Actin Cortex ◽  
Ventral Furrow ◽  
Delayed Initiation ◽  
Apical Area

During development, coordinated cell shape changes alter tissue shape. In the Drosophila ventral furrow and other epithelia, apical constriction of hundreds of epithelial cells folds the tissue. Genes in the Gα12/13 pathway coordinate collective apical constriction, but the mechanism of coordination is poorly understood. Coupling live-cell imaging with a computational approach to identify contractile events, we discovered that differences in constriction behavior are biased by initial cell shape. Disrupting Gα12/13 exacerbates this relationship. Larger apical area is associated with delayed initiation of contractile pulses, lower apical E-cadherin and F-actin levels, and aberrantly mobile Rho-kinase structures. Our results suggest that loss of Gα12/13 disrupts apical actin cortex organization and pulse initiation in a size-dependent manner. We propose that Gα12/13 robustly organizes the apical cortex despite variation in apical area to ensure the timely initiation of contractile pulses in a tissue with heterogeneity in starting cell shape.

scholarly journals Hyperactivation of the folded gastrulation pathway induces specific cell shape changes

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 589-597 ◽  
Author(s):  
P. Morize ◽  
A.E. Christiansen ◽  
M. Costa ◽  
S. Parks ◽  
E. Wieschaus
Keyword(s):  
Cell Shape ◽  
Inducible Promoter ◽  
Specific Cell ◽  
Apical Surface ◽  
Apical Constriction ◽  
Cellular Effects ◽  
Ventral Furrow ◽  
Cell Shape Changes ◽  
Shape Changes

During Drosophila gastrulation, mesodermal precursors are brought into the interior of the embryo by formation of the ventral furrow. The first steps of ventral furrow formation involve a flattening of the apical surface of the presumptive mesodermal cells and a constriction of their apical diameters. In embryos mutant for folded gastrulation (fog), these cell shape changes occur but the timing and synchrony of the constrictions are abnormal. A similar phenotype is seen in a maternal effect mutant, concertina (cta). fog encodes a putative secreted protein whereas cta encodes an (alpha)-subunit of a heterotrimeric G protein. We have proposed that localized expression of the fog signaling protein induces apical constriction by interacting with a receptor whose downstream cellular effects are mediated by the cta G(alpha)protein. <P> In order to test this model, we have ectopically expressed fog at the blastoderm stage using an inducible promoter. In addition, we have examined the constitutive activation of cta protein by blocking GTP hydrolysis using both in vitro synthesized mutant alleles and cholera toxin treatment. Activation of the fog/cta pathway by any of these procedures results in ectopic cell shape changes in the gastrula. Uniform fog expression rescues the gastrulation defects of fog null embryos but not cta mutant embryos, arguing that cta functions downstream of fog expression. The normal location of the ventral furrow in embryos with uniformly expressed fog suggests the existence of a fog-independent pathway determining mesoderm-specific cell behaviors and invagination. Epistasis experiments indicate that this pathway requires snail but not twist expression.

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