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PubMed1999

Circumferential migration of ameboid microglia in the margin of the developing quail retina.

Central-to-peripheral migration of QH1-positive microglial precursors occurs in the vitrealmost part of the developing quail retina. This study shows that some QH1-positive ameboid cells with morphological features of migrating cells are already present in the margin of the retina before microglial precursors migrating centrally to peripherally arrive in this zone. Because the earlier cells are oriented parallel to the ora serrata, we deduce that some microglial cells migrate circumferentially in the margin of the retina, whereas other microglial precursors migrate from central to peripheral zones. Microglial cells that migrate circumferentially are first seen on embryonic day 6 (E6) and advance in a temporal-to-dorsal-to-nasal direction from the temporoventral quadrant of the retina. When cells migrating centrally to peripherally reach the retinal margin, they meet those migrating circumferentially. From E6 on, some QH1-positive dendritic cells in the ciliary body bear processes that penetrate the retina, where they are oriented circumferentially. These observations suggest that microglial cells that migrate circumferentially in the retinal margin share a common origin with dendritic cells of the ciliary body. Therefore, microglial cells of the quail retina appear to make up a heterogeneous population, with some cells originating from the pecten/optic nerve head area and others from the ciliary body.

Aging↗

PubMed1998

CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize beta1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion.

Cell migration may depend on integrin-mediated adhesion to and deadhesion from extracellular matrix ligands. This concept, however, has not yet been confirmed for T lymphocytes migrating in three-dimensional extracellular matrices. We investigated receptor involvement in T cell migration combining a three-dimensional collagen matrix model with time-lapse videomicroscopy, computer-assisted cell tracking and confocal microscopy. In collagen lattices, the migration of CD4+ T cells (1) involved interactions with collagen fibers at the leading edge and uropod likewise, (2) occurred independently of the co-clustering of beta1, beta2, or beta3 integrins with F-actin, focal adhesion kinase, and phosphotyrosine at interactions with collagen fibers, (3) was counteracted by high-affinity beta1 integrin binding induced by antibody TS2/16; however, (4) the migration could not be blocked by a combination of adhesion-perturbing anti-beta1, -beta2, -beta3, and alpha v integrin antibodies. Integrin blocking neither affected cell polarization, interaction with fibers, beta1 integrin distribution, migration velocity, path structure, nor the number of locomoting cells in spontaneously migrating or concanavalin A-activated cells. Hence, T lymphocytes migrating in three-dimensional collagen matrices may utilize highly transient interactions with collagen fibers of low adhesivity, thereby differing from focal adhesion-dependent migration strategies employed by other cells.

Antibodies, Monoclonal↗

PubMed2001

Stimulation of epithelial tissue migration by certain porous topographies is independent of fluid flux.

A surface with columnar pores 0.1 or 0.4 microm in diameter is shown to have a novel effect on the migration of corneal epithelial tissue sheets; migration is stimulated in a nondirectional manner with respect to migration over a planar, nonporous surface (Dalton, Evans, McFarland, and Steele, J Biomed Mater Res 1999;45:384-394; Steele, Johnson, McLean, Beumer, and Griesser, J Biomed Mater Res 2000;50:475-482). By blind-ending the pores, we show that this increase in tissue migration is not dependent on fluid flux through the pores and so appears to occur as a result of surface topography. From transmission electron micrographs, the migrating tissue appears to form either close contacts or focal adhesions at the edge of some pore channels; we speculate that this may provide a fulcrum for the enhanced migration. Scanning electron micrographs suggest that within tissue that migrates over the surfaces that contain blind-ended pores, the cells are more extensively spread than those in tissue migrating on a planar surface. The migration of disaggregated epithelial cells is enhanced on surfaces that contain 0.1- or 0.4-microm-diameter pores (compared with a planar surface), and this is similarly independent of fluid flux.

Animals↗

PubMed1984

Peptide fragments of laminin and fibronectin promote migration (haptotaxis and chemotaxis) of metastatic cells.

The migration of tumour cells through basement membranes and extracellular matrices is an integral component of tumour invasion and metastasis. Laminin (LMN) and fibronectin (FN) at 1-100 micrograms/ml promote the directed migration of metastatic murine melanoma cells 40-70-fold greater than controls in modified Boyden chambers. Antibodies abrogated the migration of cells in response to the respective protein. Preincubation of melanoma cells with plasma FN had no effect on subsequent migration to LMN or FN. The migration of these cells was largely related to substratum-attached molecules and increasing adhesion gradients of cells; this has been termed haptotaxis. Peptide fragments of both FN and LMN were isolated by affinity chromatography with monoclonal antibodies, heparin or other constituents. FN has two unique domains, 80-125 K and 66 K, which promote the adhesion of tumour cells, whereas only one appeared to be responsible for promoting migration. Peptides of LMN, isolated with heparin and monoclonal antibody, define a cell migration-promoting activity within the 200 K chains of LMN. Serum spreading factor and epinectin, the latter an adhesion molecule derived from squamous epithelial tumour cells, are also capable of promoting the migration of malignant cells. Thus, directed migration of metastatic tumour cells may be promoted with peptide fragments of adhesion molecules and blocked with the respective antibody.

Animals↗

PubMed1996

Effects of nitric oxide on chondrocyte migration, adhesion, and cytoskeletal assembly.

OBJECTIVE: The migration of cells of chondrocyte lineage is believed to play a role in cartilage growth and repair. The present study examined 1) whether chondrocytes are capable of migration in vitro; and 2) the effects of nitric oxide (NO) on chondrocyte migration, adhesion, and cytoskeletal assembly. METHODS: Chondrocyte migration was evaluated by 2 assays: 1) "centrifugal" migration within a 3-dimensional collagen matrix (dot culture); and 2) directed migration under agarose in response to bone morphogenetic protein. To assess the effects of NO, chondrocytes were treated with either exogenous NO (S-nitrosoglutathione [SNO-GSH]) or a mixture of cytokines known to induce endogenous NO production. The effects of NO on chondrocyte adhesion to fibronectin-coated surfaces, as well as on actin polymerization (determined by indirect immunofluorescence), were also examined. RESULTS: The capacity of chondrocytes to migrate was demonstrated both by the dot culture and by agarose methods. Both SNO-GSH and endogenous NO induced by cytokines inhibited this migration. Exposure to NO also inhibited attachment of chondrocytes to fibronectin and disrupted assembly of actin filaments. These effects of SNO-GSH and cytokine-induced NO production were reversed in the presence of hemoglobin and the NO synthase inhibitor NG-monomethyl arginine, respectively. CONCLUSION: NO interferes with chondrocyte migration and attachment to fibronectin, an extracellular matrix protein, probably via effects on the actin cytoskeleton. These effects of NO may result in impairment of cartilage repair, by interfering with the extracellular matrix regulation of chondrocyte function.

Animals↗

PubMed2006

Migration of bone marrow stromal cells in 3D: 4 color methodology reveals spatially and temporally coordinated events.

The cytoskeleton plays a central role in many cell processes including directed cell migration. Since most previous work has investigated cell migration in two dimensions (2D), new methods are required to study movement in three dimensions (3D) while preserving 3D structure of the cytoskeleton. Most previous studies have labeled two cytoskeletal networks simultaneously, impeding an appreciation of their complex and dynamic interconnections. Here we report the development of a 4 color method to simultaneously image vimentin, actin, tubulin and the nucleus for high-resolution confocal microscopy of bone-marrow stromal cells (BMSCs) migrating through a porous membrane. Several methods were tested for structural preservation and labeling intensity resulting in identification of an optimized simultaneous fixation and permeabilization method using glutaraldehyde, paraformaldehyde and Triton X-100 followed by a quadruple fluorescent labeling method. This procedure was then applied at a sequence of time points to migrating cells, allowing temporal progression of migration to be assessed by visualizing all three networks plus the nucleus, providing new insights into 3D directed cell migration including processes such as leading edge structure, cytoskeletal distribution and nucleokinesis. Colocalization of actin and microtubules with distinct spatial arrangements at the cellular leading edge during migration, together with microtubule axial polarization supports recent reports indicating the pivotal role of microtubules in directed cell migration. This study also provides a foundation for 3D migration studies versus 2D studies, providing precise and robust methods to attain new insights into the cellular mechanisms of motility.

Actins↗

PubMed1994

Role of microtubules in random cell migration: stabilization of cell polarity.

The role of microtubules in random cell migration was investigated using time-lapse videomicroscopy to record in vitro the shape and motile behavior of guinea pig alveolar macrophages before and after disrupting microtubules with colcemid. Cell migration was quantified in terms of directional persistence time and speed. Motility was also correlated with morphological polarity: cells having a single lamellipodal region (monopolar cells) migrated, whereas those lacking a lamellipod (apolar cells) or with opposing lamellipodal regions (bipolar cells) did not migrate. Within 2 hours, colcemid caused a shift in polarity from 80% monopolar cells to 40% monopolar and 40% bipolar cells and a corresponding decrease from 80% to 40% in the fraction of migrating cells. Mean persistence time and speed decreased only slightly (approximately 20%) for those cells (still monopolar) which continued to migrate in the presence of colcemid. Persistence time and speed actually increased for many individual cells, indicating that random migration did not require intact microtubules. We conclude that colcemid treatment destabilizes monopolarity, leading to the gradual loss of monopolarity and consequent inhibition of migration. While a cell remains monopolar, it will continue to migrate even in the absence of intact microtubules, but microtubules are required for the long-term maintenance of cellular monopolarity and, thus, for continued motility.

Animals↗

PubMed1994

Characteristics of pronuclear migration in Beroe ovata.

In the large eggs (approximately 1 mm) of the ctenophore Beroe ovata, female pronuclei migrate long distances to join stationary male pronuclei in the peripheral cytoplasm that surrounds the yolky interior. We have investigated the mechanism of nuclear migration using time lapse video recording, automated image analysis, visualization of microtubules by immunofluorescence and rhodamine-tubulin injection, and electron microscopy. Female pronuclei migrated at average speeds of 0.2 microns/sec, and were found to show periodic oscillations in velocity. Alternating phases of acceleration and deceleration occurred with an average periodicity of 235 seconds covering distances of 47 microns (about 3 times the nuclear diameter). Migration velocities and velocity oscillations were similar in fertilized and unfertilized eggs; however, changes in migration direction were much more frequent in unfertilized eggs. Characteristic deformations of the pronuclear membrane and occasional rotation of the nuclear contents were observed during migration. Inhibitor studies indicated that microtubules are required for nuclear migration. In fertilized eggs the top of the nucleus was found to move through the dense layer of aligned sperm aster microtubules. The frequent changes in direction of pronuclear migration in unfertilized eggs reflect the random organization of the microtubule layer in the absence of sperm derived centrosomes. Densely packed endoplasmic reticulum was found intermeshed with sperm aster microtubules and connected extensively with the nuclear membrane during migration. Most nuclear pores were grouped in an infolding of the nuclear membrane. We suggest that in fertilized eggs the female pronucleus is transported to the minus ends of sperm aster microtubules using motor molecules attached either to the outer nuclear membrane and/or to the network of connecting ER.

Animals↗

PubMed2004

Radial glia produce and align the ligand fibronectin during neuronal migration in the developing chick brain.

We demonstrated previously that alpha8beta1 integrin regulates the migration and survival of immature neurons during development of the chicken optic tectum; however, the potential extracellular ligand was unknown. We used immunohistochemistry to determine if several potential ligands (fibronectin, tenascin, vitronectin, and osteopontin) were expressed during neuronal migration along radial glia (RG). Fibronectin was localized in a pattern relevant to radial migration and survival of neurons; it was present before and during neuronal migration and appeared oriented along RG fibers by conventional fluorescence microscopy. Confocal microscopy confirmed that fibronectin was localized along RG cells during radial migration. It was more concentrated in some superficial laminae, which might support directional movement. Fibronectin was present after formation of definitive tectal laminae, but was diffuse and not aligned along RG, which persist. Flow cytometry analysis of dissociated optic tectum cells revealed that almost all RG were positive for fibronectin. Short-term cell culture experiments using an exocytosis inhibitor revealed that fibronectin accumulated in most RG cells. Thus, fibronectin is produced by RG and is aligned along their surfaces before and during migration. Fibronectin, therefore, is a potential ligand for general radial neuronal migration in the chick optic tectum. Its predominant source appears to be RG, in contrast with developing mammalian cortex, where fibronectin was not found in a pattern that could guide widespread radial migration and where neurons are the predominant producers of fibronectin during migration.

Animals↗

PubMed1993

Orderly migration of neurons to the principal sensory nucleus of the trigeminal nerve of the rat.

As nuclei in the central nervous system develop, neurons actively migrate from their site of generation to their permanent residence. This study examines the spatiotemporal sequence of the migration of neurons to the principal sensory nucleus of the trigeminal nerve (PSN) of the rat. Tritiated thymidine autoradiography and bromodeoxyuridine immunohistochemistry were used to examine the spatiotemporal patterns of migration of PSN neurons born on gestational day (G) 12 (early-generated neurons) and of those born on G14 (late-generated neurons). The final residence of early- and late-generated neurons was determined by injecting a thymidine analog into a pregnant rat on G12 or G14 and sacrificing the pups on postnatal day (P) 30. Early- and late-generated neurons were distributed medially and laterally, respectively. The schedule of the migration of PSN neurons was also determined. A few pioneer neurons born on G12 reached the PSN by G14; however, the last of the neurons born on G12 arrived in the PSN by G18. The migration of neurons born on G14 was completed 2-6 days later than that of the early-generated neurons. The path followed by migrating neurons was delineated by radial glial fibers. These processes were identified in the developing metencephalon by RAT-401 immunohistochemistry. Radial glial fibers extended from the lateral part of the ventricular zone through the tegmentum and the PSN to the surface of the metencephalon external to the sensory tract of the trigeminal nerve. RAT-401-immunoreactive processes were detected during the period of neuronal migration, but disappeared by P5. Thus, the migration of PSN neurons follows an inside-to-outside sequence, which apparently is organized by radial glial fibers. The inside-to-outside sequence of neuronal migration directly opposes the outside-to-inside gradient of synaptogenesis.

Animals↗

PubMed2002

Synthetic matrix metalloproteinase inhibitor decreases early cardiac neural crest migration in chicken embryos.

During early embryonic development, cardiac neural crest (NC) cells emerge from the forming neural tube, migrate beneath the ectoderm, enter the pharyngeal arches, and subsequently participate in the septation of the heart. Like tumor cells, NC cells penetrate through basement membranes and invade extracellular matrix during their emigration and migration and, therefore, are liable to use similar invasive mechanisms. Matrix metalloproteinases (MMPs) are a family of zinc proteolytic enzymes known to be important in cell migration and invasion of normal and metastatic cells. In an earlier study, we found that the spatial and temporal distribution pattern of MMP-2 positively correlates with cardiac NC migration, suggesting MMP enzymatic activity may be important in mediating cardiac cell NC migration. To test this hypothesis, a synthetic MMP inhibitor, KB8301, was used to block MMP enzymatic activity during in vitro and in vivo cardiac NC cell migration in chick embryos. Injection of KB8301 into the cell-free space adjacent to the neural tube at the level of the second somite before the NC cells emigrated caused major morphologic anomalies in embryos and disrupted cardiac NC morphogenesis. Unilateral injection of KB8301 at lower concentrations, significantly decreased cardiac NC migration on the injected side compared with the noninjected side and compared with that of the injected controls. This decrease correlated with a decrease in MMP activity in the embryos and was not attributable to differences in embryo size or rate of embryonic development after injection. KB8301 also significantly decreased the rate of NC cell motility and distance NC cells migrated from explanted neural tubes and increased cell area and perimeter. These data suggest that MMP enzymatic activity is an important mediator of early cardiac NC migration and that perturbation of endogenous MMP activity may lead to NC-related congenital defects.

Animals↗

PubMed2007

Effect of Gdnf haploinsufficiency on rate of migration and number of enteric neural crest-derived cells.

The enteric nervous system arises predominantly from vagal level neural crest cells that migrate into the foregut and then colonize the entire length of the gastrointestinal tract. Previous studies have demonstrated that glial cell line-derived neurotrophic factor (GDNF) promotes the migration of enteric neural crest-derived cells (ENCs) in vitro, but a role for GDNF in the migration of ENCs in vivo has yet to be demonstrated. In this study, the effects of Gdnf haploinsufficiency on ENC rate of migration and number during mid embryonic development were examined. Although the entire gut of embryonic Gdnf(+/-) mice was colonized, a significant delay in the migration of ENCs along the embryonic hindgut was found. However, significant effects of Gdnf haploinsufficiency on ENC number were detected before the stage at which migration defects were first evident. As previous studies have shown a relationship between ENC number and migration, the effects of Gdnf haploinsufficiency on migration may be due to an indirect effect on cell number and/or a direct effect of GDNF on ENC migration. Gdnf haploinsufficiency did not cause any detectable change in the rate of neuronal differentiation of ENCs.

Animals↗

PubMed1990

Mutations affecting embryonic cell migrations in Caenorhabditis elegans.

Four recessive mutations that affect long-range embryonic migration of the two canal-associated neurons (CANs) in C. elegans were isolated and characterized with the goal of identifying genes involved in control of directed cell movement. Mutant animals were identified initially by their "withered" tails, a phenotype associated with abnormal CAN migration; the mutants were then analyzed for abnormal cell migrations by Nomarski microscopy. Based on genetic complementation tests, the mutations were assigned to four different loci, two new (mig-10 III, mig-11 III) and two previously identified (unc-39 V, vab-8 V). Mutations at all four loci affect CAN migration with high to moderate penetrance (the percentage of mutant animals that exhibit the phenotype). In addition, two other bilaterally symmetric pairs of neurons (ALM and HSN), the mesoblast M, and a pair of coelomocyte mother cells are affected by one or more of the mutations, generally with lower penetrance. With the exceptions of HSN and the right coelomocyte mother cell, which occasionally migrate beyond their normal destinations, the cells affected appear to migrate either incompletely or not at all. All the migration phenotypes show incomplete penetrance and variable expressively, although genetic tests suggest that mutations at mig-10 and vab-8 result in complete or nearly complete loss of gene function. The variability in mutant phenotypes allowed tests for interdependence of several of the affected migrations; all those analyzed appeared independent of one another. The possible nature of the mutant defects and possible roles of these four loci in cell migration are discussed.

Animals↗

PubMed2006

Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis.

Glioma cells have a remarkable capacity to infiltrate the brain and migrate long distances from the tumor, making complete surgical resection impossible. Yet, little is known about how glioma cells interact with the complex microenvironment of the brain. To investigate the patterns and dynamics of glioma cell infiltration and migration, we stereotactically injected eGFP and DsRed-2 labeled rat C6 glioma cells into neonatal rat forebrains and used time-lapse microscopy to observe glioma cell migration and proliferation in slice cultures generated from these brains. In this model, glioma cells extensively infiltrated the brain by migrating along the abluminal surface of blood vessels. Glioma cells intercalated their processes between the endothelial cells and the perivascular astrocyte end feet, but did not invade into the blood vessel lumen. Dynamic analysis revealed notable similarities between the migratory behavior of glioma cells and that previously observed for glial progenitor cells. Glioma cells had a characteristic leading process and migrated in a saltatory fashion, with bursts of migration separated by periods of immobility, and maximum speeds of over 100 microm/h. Migrating glioma cells proliferated en route, pausing for as short as an hour to divide before the daughter cells resumed migrating. Remarkably, the majority of glioma cell divisions took place at or near vascular branch points, suggesting that mitosis is triggered by local environmental cues. This study provides the first dynamic analysis of glioma cell infiltration in living brain tissue and reveals that the migration and proliferation of transplanted glioma cells is directed by interactions with host brain vasculature.

Animals↗

PubMed2006

Glial cell line-derived neurotrophic factor promotes olfactory ensheathing cells migration.

Olfactory ensheathing cells (OECs) are a unique type of macroglia with axonal growth-promoting properties. The migrating ability of OECs in CNS is essential for neural regeneration. However, little is known about the extracellular and intracellular factors that regulate OEC migration. In the present study, we examined the effects of glial cell line-derived neurotrophic factor (GDNF) on OECs migration. Initially, the "scratch" migration assay, Boyden chamber assay, and explant migration assay showed that GDNF could promote OECs migration in vitro. Treatment of OECs with GDNF also induced cytoskeleton reorganization and up-regulated expression of cytoskeleton proteins. GDNF-induced OECs migration was demonstrated depending on GFRalpha-1 and Ret receptor, and activation of JNK and Src signaling cascades. Furthermore, GDNF was found to promote implanted OECs migration in a spinal cord hemisection injury model. Together, we report, to our knowledge for the first time, that GDNF stimulate OECs migration in vitro and in vivo.

Actin Cytoskeleton↗

PubMed1992

Migration of grafted rat astrocytes: dependence on source/target organ.

Neonatal rat cortical astrocytes migrate extensively after transplantation into the brains of adult hosts. However, the effects of cues provided by different sources of donor astrocytes and by different target sites of implantation on this migration is unknown. In order to investigate the significance of regional influences on glial migration, we established primary cultures of astrocytes derived from 1-3 day old rat cerebral cortex, hippocampus, and hypothalamus. After in vitro labelling with either Fast Blue or fluorescein-labelled latex beads, these astrocytes were inoculated into different target regions of the adult rat brain by stereotaxic injection with a Hamilton syringe. Astrocytes implanted into the cerebral cortex migrated extensively throughout the adult brain regardless of their donor source. These implanted cells were intimately associated with the ventricular wall, glial limitans, vasculature, and fiber bundles. Astrocytes homografted into the hippocampus and the hypothalamus migrated primarily within and around the respective homotopic target organs. Migration of astrocytes derived from cerebral cortex was also limited when injections were made into these two regions. In these latter cases, migration appeared to be less guided by other cellular or regional cues than was migration after implantation into the cerebral cortex. These results suggest that the migration patterns of astrocytes grafted after tissue culture are more dependent on the target implantation site than on the donor organ.

Animals↗

PubMed2003

Nitric oxide-mediated promotion of mammary tumour cell migration requires sequential activation of nitric oxide synthase, guanylate cyclase and mitogen-activated protein kinase.

Using clonal derivatives of spontaneous mammary tumours in C3H/HeJ mice, we had earlier shown that tumour-derived nitric oxide (NO), resulting from endothelial type (e) NO synthase (NOS) expression by tumour cells, promoted tumour growth and metastasis by multiple mechanisms: stimulation of tumour cell invasiveness, migration and angiogenesis. Our present study examined the signaling mechanisms underlying NO-mediated promotion of tumour cell migration in a highly metastatic and high eNOS-expressing C3H/HeJ mammary tumour cell line, C3L5. C3L5 cell migration was reduced in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor) in a concentration-dependent manner and restored in the additional presence of excess L-arginine (NOS substrate), confirming a migration-promoting role of endogenous NO. Migratory capacity of C3L5 cells was reduced after treatment with the guanylate cyclase (GC) inhibitor 1-H-[1,2,4]oxadiaxolo[4,3-a]quinolalin-1-one (ODQ) and restored in the additional presence of 8-bromoguanosine 3'5'-cyclic monophosphate (8-Br cGMP, cGMP analogue), demonstrating a pivotal role for GC in C3L5 cell migration. Mitogen-activated protein kinase kinase (MAPKK; MEK) inhibitor, UO126, blocked migration, demonstrating MEK involvement in C3L5 cell migration. Furthermore, both ODQ and UO126 blocked migration-restoring effects of L-arginine in L-NAME-treated cells, indicating that GC and MAPK pathways are required for endogenous NO-mediated migratory responses. Similarly, L-NAME reduced and additional treatment with excess L-arginine or sodium nitroprusside (SNP, NO donor) stimulated phosphorylation of extracellular signal-regulated kinases (ERK(1/2)), demonstrating a role for endogenous and exogenous NO in ERK(1/2) activation. ODQ inhibited ERK(1/2) activation, whereas 8-Br cGMP stimulated ERK(1/2) phosphorylation in L-NAME-treated cells, indicating that cGMP is a downstream effector of NOS for ERK(1/2) activation. Finally, both ODQ and UO126 blocked the capacity of L-arginine to restore ERK(1/2) phosphorylation in L-NAME-treated cells, demonstrating that GC and MEK are both required for endogenous NO-mediated MAPK activation. Together, these results indicate sequential activation of NOS, GC and MAPK pathways in mediating signals for C3L5 cell migration, an essential step in invasion and metastasis. Since NOS activity is positively associated with human breast cancer progression, the present results are relevant for development of therapeutic modalities for this disease.

Animals↗

PubMed2006

Migration of F9 parietal endoderm cells is regulated by the ERK pathway.

Cell migration is regulated by the action of many signaling pathways that are activated in specific regions of migrating cells. Extracellular regulated kinase 1/2 (ERK) signaling can modulate the migration of cells by controlling the turnover of focal adhesions and the dynamics of actin polymerization. Focal adhesion turnover is necessary for cell migration, and the formation of strong actin stress fibers and mature focal adhesions puts the brakes on cell migration. We used F9 wild-type and vinculin null (vin-/-) parietal endoderm (PE) outgrowth to study the role of the ERK signaling pathway in cell migration. Upon plating of F9 embryoid bodies (EBs) onto laminin-coated dishes, PE cells migrate away from the EBs, providing an in vitro model for studying directed migration of this embryonic cell type. Our results suggest that the ERK pathway regulates PE cell migration by affecting the formation of focal adhesions and lamellipodia through the action of myosin light chain kinase (MLCK).

Animals↗