scholarly journals Requirement of Pax6 for the integration of guidance cues in cell migration

2017 ◽  
Vol 4 (10) ◽  
pp. 170625 ◽  
Author(s):  
Miguel Arocena ◽  
Ann M. Rajnicek ◽  
Jon Martin Collinson
Keyword(s):  
Cell Migration ◽  
Electric Fields ◽  
Neural Development ◽  
Mouse Embryos ◽  
Contact Guidance ◽  
Wild Type ◽  
General Direction ◽  
Vast Array ◽  
Guidance Cues ◽  
Flat Substrate

The intricate patterns of cell migration that are found throughout development are generated through a vast array of guidance cues. Responding integratively to distinct, often conflicting, migratory signals is probably crucial for cells to reach their correct destination. Pax6 is a master transcription factor with key roles in neural development that include the control of cell migration. In this study, we have investigated the ability of cells derived from cortical neurospheres from wild-type (WT) and Pax6 −/− mouse embryos to integrate diverging guidance cues. We used two different cues, either separately or in combination: substratum nanogrooves to induce contact guidance, and electric fields (EFs) to induce electrotaxis. In the absence of an EF, both WT and Pax6 −/− cells aligned and migrated parallel to grooves, and on a flat substrate both showed marked electrotaxis towards the cathode. When an EF was applied in a perpendicular orientation to grooves, WT cells responded significantly to both cues, migrating in highly oblique trajectories in the general direction of the cathode. However, Pax6 −/− cells had an impaired response to both cues simultaneously. Our results demonstrate that these neurosphere derived cells have the capacity to integrate diverging guidance cues, which requires Pax6 function.

Electric fields, contact guidance and the direction of nerve growth

Development ◽  
1986 ◽  
Vol 94 (1) ◽  
pp. 245-255
Author(s):  
Colin D. McCaig
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Applied Electric Field ◽  
Free Choice ◽  
Contact Guidance ◽  
Orthogonal Direction ◽  
Nerve Growth ◽  
Guidance Cues

Nerve orientation in response to electrical guidance cues in one direction and contact guidance cues in an orthogonal direction has been studied. Where neurites had a free choice between following contact guidance cues or electrical cues, the direction of nerve growth was determined predominantly by the vector of the applied electric field.

Studies of t6/t6 mouse embryos

Development ◽  
1975 ◽  
Vol 33 (3) ◽  
pp. 697-713
Author(s):  
Mary Nadijcka ◽  
Nina Hillman
Keyword(s):  
Lipid Droplets ◽  
Mouse Embryos ◽  
Wild Type ◽  
Electron Microscopic ◽  
Homozygous Mouse ◽  
Cytoplasmic Lipid Droplets

The phenocritical period of the t6/t6 genome extends from the late blastocyst substages through the elongated egg-cylinder stage, whereas the lethal period begins at the short egg-cylinder-stage and extends through the elongated egg-cylinder stage. Most of the homozygous mouse embryos die during the short egg-cylinder stage. The viable egg-cylinder-staged t6/t6 embryos can be distinguished from their phenotypically wild-type litter-mates at both the light and electron microscopic levels. The distinguishing characteristics of these embryos are aberrantly arranged entodermal cells, excessive cytoplasmic lipid and crystal-containing mitochondria. These same features are also characteristic of those mutant embryos which are developmentally arrested at both the short and elongated egg-cylinder stages. Over 50% of the t6/t6 embryos can be identified as early as the late blastocyst substages by the presence of large, electron-dense cytoplasmic lipid droplets.

Abstract 1042: Viral Chemokine Modulating Protein, M-T7, Interrupts Chemokine : Glycosaminoglycan (GAG) Interaction: M-T7 Inhibitory Activity is Dependent upon Y46 and V210 aminoacid residues

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Erbin Dai ◽  
Dana McIvor ◽  
Liying Liu ◽  
Ganesh Munaswamy-Ramanujam ◽  
Yunming Sun ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Invasion ◽  
Inhibitory Activity ◽  
Active Sites ◽  
Point Mutations ◽  
List Type ◽  
Wild Type ◽  
Monocyte Activation ◽  
Cc Chemokine ◽  
Plaque Growth

Background: Chemokines bind to glycosaminoglycans (GAGs) forming gradients that direct inflammatory cell invasion. The viral chemokine modulating protein (CMP), MT-7 binds the C terminal, GAG-binding domain of chemokines and has been previously reported to significantly reduce cell invasion and plaque growth in rat aortic and renal transplant models. Two other viral CMPs, M-T1 and M3 CMPs bind the N terminal domain of chemokines that bind to cell surface receptors. To determine the role of CC chemokine receptor 2 (CCR2) and GAGs for M-T7 anti-inflammatory activity, effects of M-T7 on plaque growth were assessed after mouse CCR2 deficient (CCR2−/−) or GAG deficient (NDST1−/−) aortic allograft transplant. Mononuclear cell migration in response to MCP-1 or RANTES into mouse ascites was also tested. Active sites necessary for M-T7 inhibition of chemokine function and monocyte activation, were assessed by infusion of in the mouse cell migration and human monocyte membrane fluidity assays. Results: M-T7 significantly reduced cell migration and intimal hyperplasia in wild type CCR2+/+ (p<0.009), and CCR2−/− aortic transplants (p<0.026). M-T1 and M3 inhibited cell invasion and plaque in CCR2+/+, but not CCR2−/− mice. M-T7 inhibited plaque growth and CC chemokine (MCP-1 and RANTES)-induced cell migration in wild type mice (P<0.01), but not in NDST1−/− mice (P=0.34). Selected M-T7 point mutations Ty (Y)46A, and Val (V) 210A no longer block chemokine-induced cell migration nor monocyte activation, whereas Asn (N) 40, Asn (N) 63 and Val (V)129 retain inhibitory activity. Conclusions: M-T7 but not M-T1 nor M3, blocks cell migration and plaque growth in CCR2 deficient (CCR2−/−) mouse aortic transplant models. M-T7 loses the ability to block cell migration and plaque growth in NDST1−/−, GAG (heparan sulfate) deficient mice. Point mutations Tyr46 and Val 210 lack inflammatory for mouse and human inflammatory monocyte responses indicating that these amino acid residues on the M-T7 CMP protein are required for inhibitory activity.

A normally attractive cell interaction is repulsive in two C. elegans mesodermal cell migration mutants

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 797-803 ◽  
Author(s):  
M.J. Stern ◽  
H.R. Horvitz
Keyword(s):  
Cell Migration ◽  
Caenorhabditis Elegans ◽  
Premature Termination ◽  
Cell Interaction ◽  
Egg Laying ◽  
Wild Type ◽  
Mesodermal Cell ◽  
C Elegans ◽  
Somatic Gonad ◽  
Sex Myoblasts

In wild-type Caenorhabditis elegans hermaphrodites, two bilaterally symmetric sex myoblasts (SMs) migrate anteriorly to flank the precise center of the gonad, where they divide to generate the muscles required for egg laying (J. E. Sulston and H. R. Horvitz (1977) Devl Biol. 56, 110–156). Although this migration is largely independent of the gonad, a signal from the gonad attracts the SMs to their precise final positions (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041–1052). Here we show that mutations in either of two genes, egl-15 and egl-17, cause the premature termination of the migrations of the SMs. This incomplete migration is caused by the repulsion of the SMs by the same cells in the somatic gonad that are the source of the attractive signal in wild-type animals.

Establishment of substratum polarity in the blastocoel roof of the Xenopus embryo

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1975-1984 ◽  
Author(s):  
M. Nagel ◽  
R. Winklbauer
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Signaling Pathways ◽  
Fibril Formation ◽  
Fgf Signaling ◽  
Matrix Assembly ◽  
Mesoderm Cell ◽  
Guidance Cues ◽  
Mesoderm Formation ◽  
Fibronectin Fibrils

The fibronectin fibril matrix on the blastocoel roof of the Xenopus gastrula contains guidance cues that determine the direction of mesoderm cell migration. The underlying guidance-related polarity of the blastocoel roof is established in the late blastula under the influence of an instructive signal from the vegetal half of the embryo, in particular from the mesoderm. Formation of an oriented substratum depends on functional activin and FGF signaling pathways in the blastocoel roof. Besides being involved in tissue polarization, activin and FGF also affect fibronectin matrix assembly. Activin treatment of the blastocoel roof inhibits fibril formation, whereas FGF modulates the structure of the fibril network. The presence of intact fibronectin fibrils is permissive for directional mesoderm migration on the blastocoel roof extracellular matrix.

Abstract 470: Recording Cell Migration Dynamics in Mouse Tissues With Cells Secreting Fluorescence Protein-tagged Collagen

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Zhongming Chen
Keyword(s):  
Cell Migration ◽  
Cell Lines ◽  
Wild Type Mouse ◽  
Cardiac Progenitor Cells ◽  
Wild Type ◽  
Mouse Tissues ◽  
Migration Dynamics ◽  
Fluorescence Protein

Background: Cell migration is an important step involved in heart regeneration and many cardiovascular diseases. However, cell migration dynamics in vivo is poorly understood due to the challenges from mammal hearts, which are opaque and fast beating, and thus individual cardiac cells cannot be imaged or tracked. Aims: In this study, cell migration dynamics in the heart is recorded with a novel strategy, in which fluorescence protein-tagged collagen is secreted from cells and deposited into extracellular matrix, forming visible trails when cells are moving in tissues. As a proof-of-concept, transplanted migration dynamics of cardiac progenitor cells in mouse hearts were investaged. Methods: Stable cell lines expressing mCherry-tagged type I collagen were generated from isolated cardiac progenitor cells, ABCG2 + CD45 - CD31 - cells (side populations), or c-kit + CD45 - CD31 - cells (c-kit + CPCs). The cell migration dynamics were monitored and measured based on the cell trails after cell transplantation into mouse tissues. Results: The stable cell lines form red cell trails both in vitro and in vivo (Fig. 1A & 1B, Green: GFP; Red: mCherry-collagen I, Blue: DAPI, bar: 50 microns). In culture dishes, the cells form visible cell trails of fluorescence protein. The cell moving directions are random, with a speed of 288 +/- 79 microns/day (side populations, n=3) or 143 +/-37 microns/day (c-kit + CPCs, n=3). After transplantation into wild-type mouse hearts, the cells form highly tortuous trails along the gaps between the heart muscle fibers. Angle between a cell trail and a muscle fiber is 16+/-16 degree (n=3). Side populations migrate twice as fast as c-kit+ CPCs in the heart (16.0 +/-8.7 microns/day vs. 8.1+/-0.0 microns/day, n=3, respectively), 18 time slower than the respective speeds in vitro . Additionally, side populations migrate significantly faster in the heart than in the skeletal muscles (26.4+/-5.8 microns/day, n=3). The side populations move significantly faster in immunodeficient mouse hearts (36.7+/-13.3 microns/day, n=3, typically used for studying cell therapies) than in wild-type mouse hearts. Conclusion: For the first time, cell migration dynamics in living hearts is monitored and examined with genetically modified cell lines. This study may greatly advance the fields of cardiovascular biology.

p21-activated kinase 1 participates in tracheal smooth muscle cell migration by signaling to p38 MAPK

2001 ◽  
Vol 281 (1) ◽  
pp. C123-C132 ◽  
Author(s):  
Melissa A. Dechert ◽  
Jennifer M. Holder ◽  
William T. Gerthoffer
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
P38 Mapk ◽  
Mammalian Cells ◽  
Muscle Cells ◽  
Mitogen Activated Protein Kinase ◽  
Tracheal Smooth Muscle ◽  
Wild Type ◽  
P21 Activated Kinase

Cell migration contributes to many physiological processes and requires dynamic changes in the cytoskeleton. These migration-dependent cytoskeletal changes are partly mediated by p21-activated protein kinases (PAKs). At least four closely related isoforms, PAK1, PAK2, PAK3, and PAK4, exist in mammalian cells. In smooth muscle cells, little is known about the expression, activation, or ability of PAKs to regulate migration. Our study revealed the existence of three PAK isoforms in cultured tracheal smooth muscle cells (TSMCs). Additionally, we constructed adenoviral vectors encoding wild type and a catalytically inactive PAK1 mutant to investigate PAK activation and its role in TSMC migration. Stimulation of TSMCs with platelet-derived growth factor (PDGF) increased the activity of PAK1 over time. Overexpression of mutant PAK1 blocked PDGF-induced chemotactic cell migration. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) in cells overexpressing wild-type PAK1 was similar to vector controls; however, p38 MAPK phosphorylation was severely reduced by overexpression of the PAK1 mutant. Collectively, these results suggest a role for PAK1 in chemotactic TSMC migration that involves catalytic activity and may require signaling to p38 MAPK among other pathways.

scholarly journals Genetic analysis of the molecular regulation of electric fields-guided glia migration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Li Yao ◽  
Teresa Shippy ◽  
Yongchao Li
Keyword(s):  
Cell Migration ◽  
Rna Sequencing ◽  
Electric Fields ◽  
Differential Expression Analysis ◽  
Cell Types ◽  
Molecular Regulation ◽  
Sequencing Data ◽  
Oligodendrocyte Precursor ◽  
Go Terms ◽  
Developing Nervous System

Abstract In a developing nervous system, endogenous electric field (EF) influence embryonic growth. We reported the EF-directed migration of both rat Schwann cells (SCs) and oligodendrocyte precursor cells (OPCs) and explored the molecular mechanism using RNA-sequencing assay. However, previous studies revealed the differentially expressed genes (DEGs) associated with EF-guided migration of SCs or OPCs alone. In this study, we performed joint differential expression analysis on the RNA-sequencing data from both cell types. We report a number of significantly enriched gene ontology (GO) terms that are related to the cytoskeleton, cell adhesion, and cell migration. Of the DEGs associated with these terms, nine up-regulated DEGs and 32 down-regulated DEGs showed the same direction of effect in both SCs and OPCs stimulated with EFs, while the remaining DEGs responded differently. Thus, our study reveals the similarities and differences in gene expression and cell migration regulation of different glial cell types in response to EF stimulation.

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