scholarly journals Endoglycan plays a role in axon guidance by modulating cell adhesion

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Thomas Baeriswyl ◽  
Alexandre Dumoulin ◽  
Martina Schaettin ◽  
Georgia Tsapara ◽  
Vera Niederkofler ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Axon Guidance ◽  
Negative Regulator ◽  
Fine Tuning ◽  
In Vivo Studies ◽  
Commissural Axons ◽  
Guidance Cue ◽  
Cell Cell

Axon navigation depends on the interactions between guidance molecules along the trajectory and specific receptors on the growth cone. However, our in vitro and in vivo studies on the role of Endoglycan demonstrate that in addition to specific guidance cue – receptor interactions, axon guidance depends on fine-tuning of cell-cell adhesion. Endoglycan, a sialomucin, plays a role in axon guidance in the central nervous system of chicken embryos, but it is neither an axon guidance cue nor a receptor. Rather, Endoglycan acts as a negative regulator of molecular interactions based on evidence from in vitro experiments demonstrating reduced adhesion of growth cones. In the absence of Endoglycan, commissural axons fail to properly navigate the midline of the spinal cord. Taken together, our in vivo and in vitro results support the hypothesis that Endoglycan acts as a negative regulator of cell-cell adhesion in commissural axon guidance.

scholarly journals Endoglycan plays a role in axon guidance and neuronal migration by negatively regulating cell-cell adhesion

2018 ◽  
Author(s):  
Thomas Baeriswyl ◽  
Alexandre Dumoulin ◽  
Martina Schaettin ◽  
Georgia Tsapara ◽  
Vera Niederkofler ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Axon Guidance ◽  
Synapse Formation ◽  
Negative Regulator ◽  
Fine Tuning ◽  
Commissural Axons ◽  
Surface Receptors ◽  
Stunted Growth ◽  
Cell Cell

SUMMARYCell migration and axon guidance are important steps in the formation of neural circuits. Both steps depend on the interactions between cell surface receptors and molecules on cells along the pathway. In addition to cell-cell adhesion, these molecular interactions provide guidance information. The fine-tuning of cell-cell adhesion is an important aspect of cell migration, axon guidance, and synapse formation.Here, we show that Endoglycan, a sialomucin, plays a role in axon guidance and cell migration in the central nervous system. In the absence of Endoglycan, commissural axons failed to properly navigate the midline of the spinal cord. In the developing cerebellum, a lack of Endoglycan prevented migration of Purkinje cells and resulted in a stunted growth of the cerebellar lobes. Taken together, these results support the hypothesis that Endoglycan acts as a ‘lubricant’, a negative regulator of cell-cell adhesion, in both commissural axon guidance and Purkinje cell migration.

scholarly journals Ultrastructural localization of E-cadherin cell adhesion molecule on the cytoplasmic membrane of keratinocytes in vivo and in vitro.

1994 ◽  
Vol 42 (10) ◽  
pp. 1333-1340 ◽  
Author(s):  
Y Horiguchi ◽  
F Furukawa ◽  
M Fujita ◽  
S Imamura
Keyword(s):  
Cell Adhesion ◽  
Free Surface ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Cytoplasmic Membrane ◽  
Ultrastructural Localization ◽  
In Vivo Studies ◽  
E Cadherin

We examined the ultrastructural localization of E (epithelial)-cadherin cell adhesion molecules by immunoperoxidase electron microscopy on the epithelium of mouse intestine, epidermis of human skin, and cultured human keratinocytes. The in vivo studies demonstrated that E-cadherin was present at the intermediate junction but not at the desmosome of the mouse intestinal single epithelium, and was found on the cytoplasmic membranes of keratinocytes with condensation in the intercellular space of the desmosomes, except for the basal surface of the basal cells. In vitro studies demonstrated that keratinocytes cultured in medium containing a low Ca2+ concentration (0.1 mM) lacked the tight connection through desmosomes, and that E-cadherin showed diffuse distribution and dot-like accumulation around the free surface of the cytoplasmic membrane. In culture medium containing a high concentration of Ca2+ (0.6 mM), keratinocytes formed desmosomal adhesion structures in which E-cadherin was accumulated. The free surface of the keratinocytes in this medium showed weaker distribution and a lesser amount of dot-like accumulation of E-cadherin than that in a low Ca2+ condition. These findings suggest that the distribution pattern of the E-cadherin cell adhesion molecules on the keratinocytes is different from that on the single epithelium of the intestine, and that E-cadherin on the cytoplasmic membrane of the keratinocytes shifts to the desmosomes under physiological conditions, participating in adhesion in association with other desmosomal cadherins.

scholarly journals In Vitro and In Vivo Studies of Biodegradability and Biocompatibility of Poly(εCL)-b-Poly(EtOEP)-Based Films

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3039
Author(s):  
Ilya Nifant’ev ◽  
Andrey Shlyakhtin ◽  
Pavel Komarov ◽  
Alexander Tavtorkin ◽  
Evgeniya Kananykhina ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Block Copolymers ◽  
Polymer Films ◽  
Hydrolytic Stability ◽  
Polymer Materials ◽  
In Vivo Studies ◽  
Cytotoxicity Test ◽  
The Impact

The control of surface bioadhesive properties of the subcutaneous implants is essential for the development of biosensors and controlled drug release devices. Poly(alkyl ethylene phosphate)-based (co)polymers are structurally versatile, biocompatible and biodegradable, and may be regarded as an alternative to poly(ethylene glycol) (PEG) copolymers in the creation of antiadhesive materials. The present work reports the synthesis of block copolymers of ε-caprolactone (εCL) and 2-ethoxy-1,3,2-dioxaphospholane-2-oxide (ethyl ethylene phosphate, EtOEP) with different content of EtOEP fragments, preparation of polymer films, and the results of the study of the impact of EtOEP/εCL ratio on the hydrophilicity (contact angle of wetting), hydrolytic stability, cytotoxicity, protein and cell adhesion, and cell proliferation using umbilical cord multipotent stem cells. It was found that the increase of EtOEP/εCL ratio results in increase of hydrophilicity of the polymer films with lowering of the protein and cell adhesion. MTT cytotoxicity test showed no significant deviations in toxicity of poly(εCL) and poly(εCL)-b-poly(EtOEP)-based films. The influence of the length of poly(EtOEP)chain in block-copolymers on fibrotic reactions was analyzed using subcutaneous implantation experiments (Wistar line rats), the increase of the width of the fibrous capsule correlated with higher EtOEP/εCL ratio. However, the copolymer-based film with highest content of polyphosphate had been subjected to faster degradation with a formation of developed contact surface of poly(εCL). The rate of the degradation of polyphosphate in vivo was significantly higher than the rate of the degradation of polyphosphate in vitro, which only confirms an objective value of in vivo experiments in the development of polymer materials for biomedical applications.

scholarly journals Mechanisms of endothelial cell coverage by pericytes: computational modelling of cell wrapping and in vitro experiments

2020 ◽  
Vol 17 (162) ◽  
pp. 20190739
Author(s):  
Kei Sugihara ◽  
Saori Sasaki ◽  
Akiyoshi Uemura ◽  
Satoru Kidoaki ◽  
Takashi Miura
Keyword(s):  
Cell Adhesion ◽  
Three Dimensional ◽  
Computational Modelling ◽  
Cellular Level ◽  
Cellular Potts Model ◽  
Contributing Factors ◽  
Modelling Framework ◽  
Cell Cell

Pericytes (PCs) wrap around endothelial cells (ECs) and perform diverse functions in physiological and pathological processes. Although molecular interactions between ECs and PCs have been extensively studied, the morphological processes at the cellular level and their underlying mechanisms have remained elusive. In this study, using a simple cellular Potts model, we explored the mechanisms for EC wrapping by PCs. Based on the observed in vitro cell wrapping in three-dimensional PC–EC coculture, the model identified four putative contributing factors: preferential adhesion of PCs to the extracellular matrix (ECM), strong cell–cell adhesion, PC surface softness and larger PC size. While cell–cell adhesion can contribute to the prevention of cell segregation and the degree of cell wrapping, it cannot determine the orientation of cell wrapping alone. While atomic force microscopy revealed that PCs have a larger Young’s modulus than ECs, the experimental analyses supported preferential ECM adhesion and size asymmetry. We also formulated the corresponding energy minimization problem and numerically solved this problem for specific cases. These results give biological insights into the role of PC–ECM adhesion in PC coverage. The modelling framework presented here should also be applicable to other cell wrapping phenomena observed in vivo .

scholarly journals Intra-cytoplasmic sperm injection in a marsupial

Reproduction ◽  
2004 ◽  
Vol 128 (5) ◽  
pp. 595-605 ◽  
Author(s):  
Nadine M Richings ◽  
Geoffrey Shaw ◽  
Peter D Temple-Smith ◽  
Marilyn B Renfree
Keyword(s):  
Cell Adhesion ◽  
Polar Body ◽  
Tammar Wallaby ◽  
Mature Oocyte ◽  
Cell Stage ◽  
Intra Cytoplasmic Sperm Injection ◽  
Polar Body Extrusion ◽  
Cell Cell

Here we report the first use of intra-cytoplasmic sperm injection (ICSI) in a marsupial, the tammar wallaby (Macropus eugenii ), to achieve in vitro fertilization and cleavage. A single epididymal spermatozoon was injected into the cytoplasm of each mature oocyte collected from Graafian follicles or from the oviduct within hours of ovulation. The day after sperm injection, oocytes were assessed for the presence of pronuclei and polar body extrusion and in vitro development was monitored for up to 4 days. After ICSI, three of four (75%) follicular and four of eight (50%) tubal oocytes underwent cleavage. The cleavage pattern was similar to that previously reported for in vivo fertilized oocytes placed in culture, where development also halted at the 4- to 8-cell stage. One-third of injected oocytes completed the second cleavage division, but only a single embryo reached the 8-cell stage. The success of ICSI in the tammar wallaby provided an opportunity to examine the influence of the mucoid coat that is deposited around oocytes passing through the oviduct after fertilization. The presence of a mucoid coat in tubal oocytes did not prevent fertilization by ICSI and the oocytes cleaved in vitro to a similar stage as follicular oocytes lacking a mucoid coat. Cell–zona and cell–cell adhesion occurred in embryos from follicular oocytes, suggesting that the mucoid coat is not essential for these processes. However, blastomeres were more closely apposed in embryos from tubal oocytes and cell–cell adhesion was more pronounced, indicating that the mucoid coat may be involved in maintaining the integrity of the conceptus during cleavage.

scholarly journals Tetraspanin CD151 maintains vascular stability by balancing the forces of cell adhesion and cytoskeletal tension

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4274-4284 ◽  
Author(s):  
Feng Zhang ◽  
Jarett E. Michaelson ◽  
Simon Moshiach ◽  
Norman Sachs ◽  
Wenyuan Zhao ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Cell Matrix ◽  
Vascular Morphogenesis ◽  
Vascular Stability ◽  
Optimal Functions ◽  
Cytoskeletal Tension ◽  
Cell Cell

Abstract Tetraspanin CD151 is highly expressed in endothelial cells and regulates pathologic angiogenesis. However, the mechanism by which CD151 promotes vascular morphogenesis and whether CD151 engages other vascular functions are unclear. Here we report that CD151 is required for maintaining endothelial capillary-like structures formed in vitro and the integrity of endothelial cell-cell and cell-matrix contacts in vivo. In addition, vascular permeability is markedly enhanced in the absence of CD151. As a global regulator of endothelial cell-cell and cell-matrix adhesions, CD151 is needed for the optimal functions of various cell adhesion proteins. The loss of CD151 elevates actin cytoskeletal traction by up-regulating RhoA signaling and diminishes actin cortical meshwork by down-regulating Rac1 activity. The inhibition of RhoA or activation of cAMP signaling stabilizes CD151-silenced or -null endothelial structure in vascular morphogenesis. Together, our data demonstrate that CD151 maintains vascular stability by promoting endothelial cell adhesions, especially cell-cell adhesion, and confining cytoskeletal tension.

scholarly journals Biogenesis of Polarized Epithelial Cells During Kidney Development In Situ: Roles of E-Cadherin–mediated Cell–Cell Adhesion and Membrane Cytoskeleton Organization

1998 ◽  
Vol 9 (11) ◽  
pp. 3161-3177 ◽  
Author(s):  
Peter A. Piepenhagen ◽  
W. James Nelson
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cells ◽  
Kidney Development ◽  
Lateral Membrane ◽  
Membrane Cytoskeleton ◽  
Triton X ◽  
E Cadherin ◽  
Cell Cell

Organization of proteins into structurally and functionally distinct plasma membrane domains is an essential characteristic of polarized epithelial cells. Based on studies with cultured kidney cells, we have hypothesized that a mechanism for restricting Na/K-ATPase to the basal-lateral membrane involves E-cadherin–mediated cell–cell adhesion and integration of Na/K-ATPase into the Triton X-100–insoluble ankyrin- and spectrin-based membrane cytoskeleton. In this study, we examined the relevance of these in vitro observations to the generation of epithelial cell polarity in vivo during mouse kidney development. Using differential detergent extraction, immunoblotting, and immunofluorescence histochemistry, we demonstrate the following. First, expression of the 220-kDa splice variant of ankyrin-3 correlates with the development of resistance to Triton X-100 extraction for Na/K-ATPase, E-cadherin, and catenins and precedes maximal accumulation of Na/K-ATPase. Second, expression of the 190-kDa slice variant of ankyrin-3 correlates with maximal accumulation of Na/K-ATPase. Third, Na/K-ATPase, ankyrin-3, and fodrin specifically colocalize at the basal-lateral plasma membrane of all epithelial cells in which they are expressed and during all stages of nephrogenesis. Fourth, the relative immunofluorescence staining intensities of Na/K-ATPase, ankyrin-3, and fodrin become more similar during development until they are essentially identical in adult kidney. Thus, renal epithelial cells in vivo regulate the accumulation of E-cadherin–mediated adherens junctions, the membrane cytoskeleton, and Na/K-ATPase through sequential protein expression and assembly on the basal-lateral membrane. These results are consistent with a mechanism in which generation and maintenance of polarized distributions of these proteins in vivo and in vitro involve cell–cell adhesion, assembly of the membrane cytoskeleton complex, and concomitant integration and retention of Na/K-ATPase in this complex.

scholarly journals A Direct Interaction of Axonin-1 with Ngcam-Related Cell Adhesion Molecule (Nrcam) Results in Guidance, but Not Growth of Commissural Axons

2000 ◽  
Vol 149 (4) ◽  
pp. 951-968 ◽  
Author(s):  
Dora Fitzli ◽  
Esther T. Stoeckli ◽  
Stefan Kunz ◽  
Kingsley Siribour ◽  
Christoph Rader ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Direct Interaction ◽  
Longitudinal Axis ◽  
Vitro Assay ◽  
Commissural Axons ◽  
Related Cell

An interaction of growth cone axonin-1 with the floor-plate NgCAM-related cell adhesion molecule (NrCAM) was shown to play a crucial role in commissural axon guidance across the midline of the spinal cord. We now provide evidence that axonin-1 mediates a guidance signal without promoting axon elongation. In an in vitro assay, commissural axons grew preferentially on stripes coated with a mixture of NrCAM and NgCAM. This preference was abolished in the presence of anti–axonin-1 antibodies without a decrease in neurite length. Consistent with these findings, commissural axons in vivo only fail to extend along the longitudinal axis when both NrCAM and NgCAM interactions, but not when axonin-1 and NrCAM or axonin-1 and NgCAM interactions, are perturbed. Thus, we conclude that axonin-1 is involved in guidance of commissural axons without promoting their growth.

scholarly journals RHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization in C. elegans

2019 ◽  
Author(s):  
Mahekta R. Gujar ◽  
Aubrie M. Stricker ◽  
Erik A. Lundquist
Keyword(s):  
Axon Guidance ◽  
Growth Cone ◽  
Neural Circuit ◽  
Growth Cones ◽  
Negative Regulator ◽  
Microtubule Organization ◽  
C Elegans ◽  
Guidance Cue ◽  
Rho Gef

AbstractUNC-6/Netrin is a conserved axon guidance cue that directs growth cone migrations in the dorsal-ventral axis of C. elegans and in the vertebrate spinal cord. UNC-6/Netrin is expressed in ventral cells, and growth cones migrate ventrally toward or dorsally away from UNC-6/Netrin. Recent studies of growth cone behavior during outgrowth in vivo in C. elegans have led to a polarity/protrusion model in directed growth cone migration away from UNC-6/Netrin. In this model, UNC-6/Netrin first polarizes the growth cone via the UNC-5 receptor, leading to dorsally biased protrusion and F-actin accumulation. UNC-6/Netrin then regulates protrusion based on this polarity. The receptor UNC-40/DCC drives protrusion dorsally, away from the UNC-6/Netrin source, and the UNC-5 receptor inhibits protrusion ventrally, near the UNC-6/Netrin source, resulting in dorsal migration. UNC-5 inhibits protrusion in part by excluding microtubules from the growth cone, which are pro-protrusive. Here we report that the RHO-1/RhoA GTPase and its activator GEF RHGF-1 inhibit growth cone protrusion and MT accumulation in growth cones, similar to UNC-5. However, growth cone polarity of protrusion and F-actin were unaffected by RHO-1 and RHGF-1. Thus, RHO-1 signaling acts specifically as a negative regulator of protrusion and MT accumulation, and not polarity. Genetic interactions suggest that RHO-1 and RHGF-1 act with UNC-5, as well as with a parallel pathway, to regulate protrusion. The cytoskeletal interacting molecule UNC-33/CRMP was required for RHO-1 activity to inhibit MT accumulation, suggesting that UNC-33/CRMP might act downstream of RHO-1. In sum, these studies describe a new role of RHO-1 and RHGF-1 in regulation of growth cone protrusion by UNC-6/Netrin.Author SummaryNeural circuits are formed by precise connections between axons. During axon formation, the growth cone leads the axon to its proper target in a process called axon guidance. Growth cone outgrowth involves asymmetric protrusion driven by extracellular cues that stimulate and inhibit protrusion. How guidance cues regulate growth cone protrusion in neural circuit formation is incompletely understood. This work shows that the signaling molecule RHO-1 acts downstream of the UNC-6/Netrin guidance cue to inhibit growth cone protrusion in part by excluding microtubules from the growth cone, which are structural elements that drive protrusion.

Eptifibatide Reduced Cell Adhesion and Recruitment Of The Myeloid Sarcoma-Inducing Leukemia Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4220-4220
Author(s):  
Jen-Fen Fu ◽  
Lee-Yung Shih
Keyword(s):  
Bone Marrow ◽  
Cell Adhesion ◽  
Leukemia Cell ◽  
Myeloid Sarcoma ◽  
Leukemia Cells ◽  
Antiplatelet Drug ◽  
Ras Gene ◽  
Cell Cell

AML patients with myeloid sarcoma (MS) usually had a poor outcome. Our clinical data revealed that AML patients harboring MLL/AF10 and RAS gene mutations were associated with MS formation. By using retroviral transduction/transplantation assay, we demonstrated that the mice transplanted with bone marrow (BM) cells carrying cooperating MLL/AF10(OM-LZ) and KRAS-G12C mutations induced MPD-like myeloid leukemia and MS. Gene expression analyses identified Gpr125, an adhesion G protein-coupled receptor, was up-regulated in the cells carrying cooperating mutations than the cells carrying MLL/AF10(OM-LZ) alone. Knockdown of Gpr125 by RNA interference reduced the number and the size of MS, suggesting that Gpr125 was involved in the MS formation. As Gpr125 contains a HormR domain with Lysine-Glycine-Aspartic acid (KGD) motif which is known to involve in the cell-extracellular matrix (ECM) and cell-cell adhesion, we investigated whether a cyclic RGD peptide drug, eptifibatide (Ep), could interfere MS formation. An in vitro cell-ECM binding assay showed that Gpr125 interacted with fibronectin. Ep reduced leukemia cell-fibronectin binding. Ep also reduced homotypic leukemia cell adhesion and leukemia cell-adipocyte adhesion. In vivo assay demonstrated that Ep reduced leukemia cells recruitment to the adipose tissues, spleen and bone marrow. Our results suggested that blocking Gpr125-mediated cell-ECM and cell-cell adhesion might be helpful to interfere MS formation and BM/spleen recruitment of leukemia cells. Disclosures: Off Label Use: Eptifibatide (Integrilin, Millennium Pharmaceuticals, also co-promoted by Schering-Plough/Essex), is an antiplatelet drug of the glycoprotein IIb/IIIa inhibitor class.

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