scholarly journals Septins are essential for protrusion and detachment in collective border cell migration

2021 ◽  
Author(s):  
Allison M Gabbert ◽  
James Mondo ◽  
Joseph P Campanale ◽  
Denise J Montell
Keyword(s):  
Cell Migration ◽  
Cell Model ◽  
Myosin Ii ◽  
Follicle Cells ◽  
Collective Cell Migration ◽  
Border Cells ◽  
Nonmuscle Myosin ◽  
Border Cell ◽  
Nonmuscle Myosin Ii

Collective cell migration is prevalent throughout development and common in metastatic tumors, yet this process is not fully understood. In this study, we explore the role of septins (Sep) in collective cell migration, using the Drosophila border cell model. We show that Sep2 and Pnut are expressed in migrating border cells and Sep1, 2, 4, and Peanut (Pnut) are required for migration. Pnut stability depends on the expression of Sep1 and Sep2 in epithelial follicle cells and migratory border cells. We show that knockdown of septins prevents normal protrusion and detachment behaviors. High resolution Airyscan imaging reveals Pnut localization in rings at the base of protrusions. While septins function independently of Cdc42, they colocalize dynamically with nonmuscle myosin II. We suggest that septin polymers may stabilize growing protrusions until sufficient myosin is recruited to retract them.

scholarly journals Fascin regulates protrusions and delamination to mediate invasive, collective cell migration in vivo

2019 ◽  
Author(s):  
Maureen C. Lamb ◽  
Kelsey K. Anliker ◽  
Tina L. Tootle
Keyword(s):  
Cell Migration ◽  
Cancer Metastasis ◽  
Collective Cell Migration ◽  
Nurse Cells ◽  
Border Cells ◽  
Border Cell ◽  
Migration Data ◽  
Border Cell Migration

AbstractFascin is an actin bundling protein that is essential for developmental cell migrations and promotes cancer metastasis. In addition to bundling actin, Fascin has several actin-independent roles. Border cell migration during Drosophila oogenesis provides an excellent model to study Fascin’s various roles during invasive, collective cell migration. Border cell migration requires Fascin. Fascin functions not only within the migrating border cells, but also within the nurse cells, the substrate for this migration. Loss of Fascin results in increased, shorter and mislocalized protrusions during migration. Data supports the model that Fascin promotes the activity of Enabled, an actin elongating factor, to regulate migration. Additionally, loss of Fascin inhibits border cell delamination. These defects are partially due to altered E-cadherin localization in the border cells; this is predicted to be an actin-independent role of Fascin. Overall, Fascin is essential for multiple aspects of this invasive, collective cell migration, and functions in both actin-dependent and -independent manners. These findings have implications beyond Drosophila, as border cell migration has emerged as a model to study mechanisms mediating cancer metastasis.

Role of nonmuscle myosin II in polyamine-dependent intestinal epithelial cell migration

1996 ◽  
Vol 270 (2) ◽  
pp. G355-G362 ◽  
Author(s):  
J. Y. Wang ◽  
S. A. McCormack ◽  
L. R. Johnson
Keyword(s):  
Cell Migration ◽  
Myosin Ii ◽  
Specific Inhibitor ◽  
Intestinal Epithelial ◽  
Nonmuscle Myosin ◽  
Nonmuscle Myosin Ii ◽  
Epithelial Cell Migration ◽  
Vitro Model

The current study determines whether nonmuscle myosin II is involved in the process requiring polyamines for the stimulation of cell migration in an in vitro model that mimics the early stages of epithelial restitution. Treatment with alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase (ODC), for 4 days totally inhibited ODC activity and depleted intracellular polyamines in the IEC-6 cells. Nonmuscle myosin II concentrations in DFMO-treated cells were decreased by 75%, and stress fibers were sparse or absent. The most striking feature of DFMO-treated cells was the appearance of many small punctate foci of myosin II in the cell interior. Migration of DFMO-treated cells was reduced by 80%. In the presence of DFMO, exogenous putrescine not only returned nonmuscle myosin II levels and distribution toward normal but also restored cell migration to control levels. The administration of wortmannin, an inhibitor of myosin light chain kinase, significantly inhibited cell migration over the denuded area in control cells and in those treated with DFMO + polyamines. These results indicate that 1) polyamine depletion by DFMO is associated with decreased concentration and reorganization of nonmuscle myosin II in IEC-6 cells and 2) exogenous spermidine reverses the inhibitory effects of DFMO.

scholarly journals Emerging Role of Nonmuscle Myosin II and Implications for NMMII Associated Deafness

2011 ◽  
Vol 145 (2_suppl) ◽  
pp. P209-P210
Author(s):  
Elliott Kozin ◽  
Bechara Kachar ◽  
Felipe Salles ◽  
Robert Adelstein ◽  
Xuefei Ma ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Nonmuscle Myosin ◽  
Nonmuscle Myosin Ii

The breathless FGF receptor homolog, a downstream target of Drosophila C/EBP in the developmental control of cell migration

Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2255-2263 ◽  
Author(s):  
A.M. Murphy ◽  
T. Lee ◽  
C.M. Andrews ◽  
B.Z. Shilo ◽  
D.J. Montell
Keyword(s):  
Cell Migration ◽  
Molecular Mechanisms ◽  
Follicle Cells ◽  
Border Cells ◽  
Timely Initiation ◽  
Fgf Receptor ◽  
Border Cell ◽  
Downstream Target ◽  
Border Cell Migration ◽  
Factor C

To investigate the molecular mechanisms responsible for the temporal and spatial control of cell movements during development, we have been studying the migration of a small group of follicle cells, called the border cells, in the Drosophila ovary. Timely initiation of border cell migration requires the product of the slow border cells (slbo) locus, which encodes the Drosophila homolog of the transcription factor C/EBP. Here we report evidence that one target of C/EBP in the control of border cell migration is the FGF receptor homolog encoded by the breathless (btl) locus. btl expression in the ovary was border cell-specific, beginning just prior to the migration, and this expression was reduced in slbo mutants. btl mutations dominantly enhanced the border cell migration defects found in weak slbo alleles. Furthermore, C/EBP-independent btl expression was able to rescue the migration defects of hypomorphic slbo alleles. Purified Drosophila C/EBP bound eight sites in the btl 5′ flanking region by DNAse I footprinting. Taken together these results suggest that btl is a key, direct target for C/EBP in the regulation of border cell migration.

Second-Site Noncomplementation Identifies Genomic Regions Required for Drosophila Nonmuscle Myosin Function During Morphogenesis

Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1845-1863
Author(s):  
Susan R Halsell ◽  
Daniel P Kiehart
Keyword(s):  
Cell Shape ◽  
Myosin Ii ◽  
Nonmuscle Myosin ◽  
Genetic Screens ◽  
Nonmuscle Myosin Ii ◽  
Cell Shape Changes ◽  
Genomic Regions ◽  
Shape Changes ◽  
Strong Interactors

Abstract Drosophila is an ideal metazoan model system for analyzing the role of nonmuscle myosin-II (henceforth, myosin) during development. In Drosophila, myosin function is required for cytokinesis and morphogenesis driven by cell migration and/or cell shape changes during oogenesis, embryogenesis, larval development and pupal metamorphosis. The mechanisms that regulate myosin function and the supramolecular structures into which myosin incorporates have not been systematically characterized. The genetic screens described here identify genomic regions that uncover loci that facilitate myosin function. The nonmuscle myosin heavy chain is encoded by a single locus, zipper. Contiguous chromosomal deficiencies that represent approximately 70% of the euchromatic genome were screened for genetic interactions with two recessive lethal alleles of zipper in a second-site noncomplementation assay for the malformed phenotype. Malformation in the adult leg reflects aberrations in cell shape changes driven by myosin-based contraction during leg morphogenesis. Of the 158 deficiencies tested, 47 behaved as second-site noncomplementors of zipper. Two of the deficiencies are strong interactors, 17 are intermediate and 28 are weak. Finer genetic mapping reveals that mutations in cytoplasmic tropomyosin and viking (collagen IV) behave as second-site noncomplementors of zipper during leg morphogenesis and that zipper function requires a previously uncharacterized locus, E3.10/J3.8, for leg morphogenesis and viability.

scholarly journals Differential role of nonmuscle myosin II isoforms during blebbing of MCF-7 cells

2017 ◽  
Vol 28 (8) ◽  
pp. 1034-1042 ◽  
Author(s):  
Sumit K. Dey ◽  
Raman K. Singh ◽  
Shyamtanu Chattoraj ◽  
Shekhar Saha ◽  
Alakesh Das ◽  
...  
Keyword(s):  
Life Cycle ◽  
Actin Filament ◽  
Myosin Ii ◽  
Nonmuscle Myosin ◽  
Nonmuscle Myosin Ii ◽  
Different Types ◽  
Membrane Protrusions ◽  
Bleb Formation ◽  
Mcf 7

Bleb formation has been correlated with nonmuscle myosin II (NM-II) activity. Whether three isoforms of NM-II (NM-IIA, -IIB and -IIC) have the same or differential roles in bleb formation is not well understood. Here we report that ectopically expressed, GFP-tagged NM-II isoforms exhibit different types of membrane protrusions, such as multiple blebs, lamellipodia, combinations of both, or absence of any such protrusions in MCF-7 cells. Quantification suggests that 50% of NM-IIA-GFP–, 29% of NM-IIB-GFP–, and 19% of NM-IIC1-GFP–expressing MCF-7 cells show multiple bleb formation, compared with 36% of cells expressing GFP alone. Of interest, NM-IIB has an almost 50% lower rate of dissociation from actin filament than NM-IIA and –IIC1 as determined by FRET analysis both at cell and bleb cortices. We induced bleb formation by disruption of the cortex and found that all three NM-II-GFP isoforms can reappear and form filaments but to different degrees in the growing bleb. NM-IIB-GFP can form filaments in blebs in 41% of NM-IIB-GFP–expressing cells, whereas filaments form in only 12 and 3% of cells expressing NM-IIA-GFP and NM-IIC1-GFP, respectively. These studies suggest that NM-II isoforms have differential roles in the bleb life cycle.

scholarly journals LIMCH1 regulates nonmuscle myosin-II activity and suppresses cell migration

2017 ◽  
Vol 28 (8) ◽  
pp. 1054-1065 ◽  
Author(s):  
Yu-Hung Lin ◽  
Yen-Yi Zhen ◽  
Kun-Yi Chien ◽  
I-Ching Lee ◽  
Wei-Chi Lin ◽  
...  
Keyword(s):  
Cell Migration ◽  
Hela Cells ◽  
Myosin Ii ◽  
Focal Adhesions ◽  
Stress Fiber ◽  
Stress Fibers ◽  
Actin Stress Fiber ◽  
Nonmuscle Myosin ◽  
Head Region ◽  
Nonmuscle Myosin Ii

Nonmuscle myosin II (NM-II) is an important motor protein involved in cell migration. Incorporation of NM-II into actin stress fiber provides a traction force to promote actin retrograde flow and focal adhesion assembly. However, the components involved in regulation of NM-II activity are not well understood. Here we identified a novel actin stress fiber–associated protein, LIM and calponin-homology domains 1 (LIMCH1), which regulates NM-II activity. The recruitment of LIMCH1 into contractile stress fibers revealed its localization complementary to actinin-1. LIMCH1 interacted with NM-IIA, but not NM-IIB, independent of the inhibition of myosin ATPase activity with blebbistatin. Moreover, the N-terminus of LIMCH1 binds to the head region of NM-IIA. Depletion of LIMCH1 attenuated myosin regulatory light chain (MRLC) diphosphorylation in HeLa cells, which was restored by reexpression of small interfering RNA–resistant LIMCH1. In addition, LIMCH1-depleted HeLa cells exhibited a decrease in the number of actin stress fibers and focal adhesions, leading to enhanced cell migration. Collectively, our data suggest that LIMCH1 plays a positive role in regulation of NM-II activity through effects on MRLC during cell migration.

scholarly journals DE-Cadherin Is Required for Intercellular Motility during Drosophila Oogenesis

1999 ◽  
Vol 144 (3) ◽  
pp. 533-547 ◽  
Author(s):  
Paulina Niewiadomska ◽  
Dorothea Godt ◽  
Ulrich Tepass
Keyword(s):  
Cell Migration ◽  
Follicle Cells ◽  
Epithelial Polarity ◽  
Border Cells ◽  
Drosophila Oogenesis ◽  
Animal Development ◽  
Border Cell ◽  
Germline Cells ◽  
Peripheral Cells ◽  
Homophilic Adhesion

Cadherins are involved in a variety of morphogenetic movements during animal development. However, it has been difficult to pinpoint the precise function of cadherins in morphogenetic processes due to the multifunctional nature of cadherin requirement. The data presented here indicate that homophilic adhesion promoted by Drosophila E-cadherin (DE-cadherin) mediates two cell migration events during Drosophila oogenesis. In Drosophila follicles, two groups of follicle cells, the border cells and the centripetal cells migrate on the surface of germline cells. We show that the border cells migrate as an epithelial patch in which two centrally located cells retain epithelial polarity and peripheral cells are partially depolarized. Both follicle cells and germline cells express DE-cadherin, and border cells and centripetal cells strongly upregulate the expression of DE-cadherin shortly before and during their migration. Removing DE-cadherin from either the follicle cells or the germline cells blocks migration of border cells and centripetal cells on the surface of germline cells. The function of DE-cadherin in border cells appears to be specific for migration as the formation of the border cell cluster and the adhesion between border cells are not disrupted in the absence of DE-cadherin. The speed of migration depends on the level of DE-cadherin expression, as border cells migrate more slowly when DE-cadherin activity is reduced. Finally, we show that the upregulation of DE-cadherin expression in border cells depends on the activity of the Drosophila C/EBP transcription factor that is essential for border cell migration.

scholarly journals GAGA Regulates Border Cell Migration in Drosophila

2020 ◽  
Vol 21 (20) ◽  
pp. 7468
Author(s):  
Anna A. Ogienko ◽  
Lyubov A. Yarinich ◽  
Elena V. Fedorova ◽  
Natalya V. Dorogova ◽  
Sergey I. Bayborodin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Migration ◽  
Target Genes ◽  
Genetic Interaction ◽  
Follicle Cells ◽  
Collective Cell Migration ◽  
Border Cells ◽  
Drosophila Oogenesis ◽  
Small Set ◽  
Multicellular Organisms

Collective cell migration is a complex process that happens during normal development of many multicellular organisms, as well as during oncological transformations. In Drosophila oogenesis, a small set of follicle cells originally located at the anterior tip of each egg chamber become motile and migrate as a cluster through nurse cells toward the oocyte. These specialized cells are referred to as border cells (BCs) and provide a simple and convenient model system to study collective cell migration. The process is known to be complexly regulated at different levels and the product of the slow border cells (slbo) gene, the C/EBP transcription factor, is one of the key elements in this process. However, little is known about the regulation of slbo expression. On the other hand, the ubiquitously expressed transcription factor GAGA, which is encoded by the Trithorax-like (Trl) gene was previously demonstrated to be important for Drosophila oogenesis. Here, we found that Trl mutations cause substantial defects in BC migration. Partially, these defects are explained by the reduced level of slbo expression in BCs. Additionally, a strong genetic interaction between Trl and slbo mutants, along with the presence of putative GAGA binding sites within the slbo promoter and enhancer, suggests the direct regulation of this gene by GAGA. This idea is supported by the reduction in the slbo-Gal4-driven GFP expression within BC clusters in Trl mutant background. However, the inability of slbo overexpression to compensate defects in BC migration caused by Trl mutations suggests that there are other GAGA target genes contributing to this process. Taken together, the results define GAGA as another important regulator of BC migration in Drosophila oogenesis.

scholarly journals Collective cell migration in development

2016 ◽  
Vol 212 (2) ◽  
pp. 143-155 ◽  
Author(s):  
Elena Scarpa ◽  
Roberto Mayor
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Collective Cell Migration ◽  
Germ Layer ◽  
Collective Migration ◽  
Developmental Models ◽  
Border Cell ◽  
Guidance Cues ◽  
Tracheal Branching

During embryonic development, tissues undergo major rearrangements that lead to germ layer positioning, patterning, and organ morphogenesis. Often these morphogenetic movements are accomplished by the coordinated and cooperative migration of the constituent cells, referred to as collective cell migration. The molecular and biomechanical mechanisms underlying collective migration of developing tissues have been investigated in a variety of models, including border cell migration, tracheal branching, blood vessel sprouting, and the migration of the lateral line primordium, neural crest cells, or head mesendoderm. Here we review recent advances in understanding collective migration in these developmental models, focusing on the interaction between cells and guidance cues presented by the microenvironment and on the role of cell–cell adhesion in mechanical and behavioral coupling of cells within the collective.

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