The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Andrew J. Copp - One of the best experts on this subject based on the ideXlab platform.
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spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by grhl2
Nature Communications, 2019Co-Authors: Evanthia Nikolopoulou, Caroline S Hirst, Christina Venturini, Dale Moulding, Abigail R Marshall, Gabriel L Galea, Ana Rolo, Sandra C. P. De Castro, Andrew J. CoppAbstract:Lack or excess expression of the surface ectoderm-expressed transcription factor Grainyhead-like2 (Grhl2), each prevent spinal neural tube closure. Here we investigate the causative mechanisms and find reciprocal dysregulation of epithelial genes, Cell Junction components and actomyosin properties in Grhl2 null and over-expressing embryos. Grhl2 null surface ectoderm shows a shift from epithelial to neuroepithelial identity (with ectopic expression of N-cadherin and Sox2), actomyosin disorganisation, Cell shape changes and diminished resistance to neural fold recoil upon ablation of the closure point. In contrast, excessive abundance of Grhl2 generates a super-epithelial surface ectoderm, in which up-regulation of Cell-Cell Junction proteins is associated with an actomyosin-dependent increase in local mechanical stress. This is compatible with apposition of the neural folds but not with progression of closure, unless myosin activity is inhibited. Overall, our findings suggest that Grhl2 plays a crucial role in regulating biomechanical properties of the surface ectoderm that are essential for spinal neurulation. Loss or over-expression of Grainyhead-like transcription factors (Grhl) prevents closure of the neural tube but the mechanism underlying this is unclear. Here, the authors show that Grhl2 regulates murine posterior-neuropore closure via changes in the identity and biomechanics of the non-neural, surface ectoderm Cells.
Ana Rolo - One of the best experts on this subject based on the ideXlab platform.
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spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by grhl2
Nature Communications, 2019Co-Authors: Evanthia Nikolopoulou, Caroline S Hirst, Christina Venturini, Dale Moulding, Abigail R Marshall, Gabriel L Galea, Ana Rolo, Sandra C. P. De Castro, Andrew J. CoppAbstract:Lack or excess expression of the surface ectoderm-expressed transcription factor Grainyhead-like2 (Grhl2), each prevent spinal neural tube closure. Here we investigate the causative mechanisms and find reciprocal dysregulation of epithelial genes, Cell Junction components and actomyosin properties in Grhl2 null and over-expressing embryos. Grhl2 null surface ectoderm shows a shift from epithelial to neuroepithelial identity (with ectopic expression of N-cadherin and Sox2), actomyosin disorganisation, Cell shape changes and diminished resistance to neural fold recoil upon ablation of the closure point. In contrast, excessive abundance of Grhl2 generates a super-epithelial surface ectoderm, in which up-regulation of Cell-Cell Junction proteins is associated with an actomyosin-dependent increase in local mechanical stress. This is compatible with apposition of the neural folds but not with progression of closure, unless myosin activity is inhibited. Overall, our findings suggest that Grhl2 plays a crucial role in regulating biomechanical properties of the surface ectoderm that are essential for spinal neurulation. Loss or over-expression of Grainyhead-like transcription factors (Grhl) prevents closure of the neural tube but the mechanism underlying this is unclear. Here, the authors show that Grhl2 regulates murine posterior-neuropore closure via changes in the identity and biomechanics of the non-neural, surface ectoderm Cells.
Evanthia Nikolopoulou - One of the best experts on this subject based on the ideXlab platform.
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spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by grhl2
Nature Communications, 2019Co-Authors: Evanthia Nikolopoulou, Caroline S Hirst, Christina Venturini, Dale Moulding, Abigail R Marshall, Gabriel L Galea, Ana Rolo, Sandra C. P. De Castro, Andrew J. CoppAbstract:Lack or excess expression of the surface ectoderm-expressed transcription factor Grainyhead-like2 (Grhl2), each prevent spinal neural tube closure. Here we investigate the causative mechanisms and find reciprocal dysregulation of epithelial genes, Cell Junction components and actomyosin properties in Grhl2 null and over-expressing embryos. Grhl2 null surface ectoderm shows a shift from epithelial to neuroepithelial identity (with ectopic expression of N-cadherin and Sox2), actomyosin disorganisation, Cell shape changes and diminished resistance to neural fold recoil upon ablation of the closure point. In contrast, excessive abundance of Grhl2 generates a super-epithelial surface ectoderm, in which up-regulation of Cell-Cell Junction proteins is associated with an actomyosin-dependent increase in local mechanical stress. This is compatible with apposition of the neural folds but not with progression of closure, unless myosin activity is inhibited. Overall, our findings suggest that Grhl2 plays a crucial role in regulating biomechanical properties of the surface ectoderm that are essential for spinal neurulation. Loss or over-expression of Grainyhead-like transcription factors (Grhl) prevents closure of the neural tube but the mechanism underlying this is unclear. Here, the authors show that Grhl2 regulates murine posterior-neuropore closure via changes in the identity and biomechanics of the non-neural, surface ectoderm Cells.
Isabelle Tardieux - One of the best experts on this subject based on the ideXlab platform.
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The toxoplasma-host Cell Junction is anchored to the Cell cortex to sustain parasite invasive force
BMC Biology, 2014Co-Authors: Marion Bichet, Candie Joly, Ahmed Hadj Henni, Thomas Guilbert, Marie Xémard, Vincent Tafani, Vanessa Lagal, Guillaume Charras, Isabelle TardieuxAbstract:Background The public health threats imposed by toxoplasmosis worldwide and by malaria in sub-Saharan countries are directly associated with the capacity of their related causative agents Toxoplasma and Plasmodium, respectively, to colonize and expand inside host Cells. Therefore, deciphering how these two Apicomplexan protozoan parasites access their host Cells has been highlighted as a priority research with the perspective of designing anti-invasive molecules to prevent diseases. Central to the mechanism of invasion for both genera is mechanical force, which is thought to be applied by the parasite at the interface between the two Cells following assembly of a unique Cell-Cell Junction but this model lacks direct evidence and has been challenged by recent genetic studies. In this work, using parasites expressing the fluorescent core component of this Junction, we analyze characteristic features of the kinematics of penetration of more than 1,000 invasion events. Results The majority of invasion events occur with a typical forward rotational progression of the parasite through a static Junction into an invaginating host Cell plasma membrane. However, if parasites encounter resistance and if the Junction is not strongly anchored to the host Cell cortex, as when parasites do not secrete the toxofilin protein and, therefore, are unable to locally remodel the cortical actin cytoskeleton, the Junction travels retrogradely with the host Cell membrane along the parasite surface allowing the formation of a functional vacuole. Kinetic measurements of the invasive trajectories strongly support a similar parasite driven force in both static and capped Junctions, both of which lead to successful invasion. However, about 20% of toxofilin mutants fail to enter and eventually disengage from the host Cell membrane while the secreted RhOptry Neck (RON2) molecules are posteriorally capped before being cleaved and released in the medium. By contrast in Cells characterized by low cortex tension and high cortical actin dynamics Junction capping and entry failure are drastically reduced. Conclusions This kinematic analysis newly highlights that to invade Cells parasites need to engage their motor with the Junction molecular complex where force is efficiently applied only upon proper anchorage to the host Cell membrane and cortex.
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BMC Biology BMC Biology The toxoplasma-host Cell Junction is anchored to the Cell cortex to sustain parasite invasive force
BMC Biology, 2014Co-Authors: Marion Bichet, Candie Joly, Ahmed Hadj Henni, Thomas Guilbert, Marie Xémard, Vincent Tafani, Vanessa Lagal, Guillaume Charras, Isabelle TardieuxAbstract:BackgroundThe public health threats imposed by toxoplasmosis worldwide and by malaria in sub-Saharan countries are directly associated with the capacity of their closely related causative agents Toxoplasma and Plasmodium, respectively to colonize and expand inside host Cells. Therefore, deciphering how these two Apicomplexan protozoan parasites access their hosting Cells has been highlighted as a high priority research with the relevant perspective of designing anti-invasive molecules to prevent diseases. Central to the mechanistic base of invasion for both genera is mechanical force, which is thought to be applied by the parasite at the interface between the two Cells following assembly of a unique Cell Junction but this model lacks direct evidence and has been challenged by recent genetic and Cell biology studies. In this work, using parasites expressing the fluorescent core component of this Junction, we analyse characteristic features of the kinematics of penetration of more than 1000 invasion events.ResultsThe majority of invasion events occur with a typical forward rotational progression of the parasite through a static Junction into a vacuole formed from the invaginating host Cell plasma membrane, in which the parasite subsequently replicates. However, if parasites encounter resistance and if the Junction is not strongly anchored to the host Cell cortex, as when parasites do not secrete the toxofilin protein and therefore are unable to locally remodel the cortical actin cytoskeleton, the Junction is capped backwards and travels retrogradely with the host Cell membrane along the parasite surface as it is enclosed within a functional vacuole. Kinetic measurements of the invasive trajectories strongly support a similar parasite driven force in both static and capped Junctions, both of which lead to successful invasion. However about 20% of toxofilin mutants fail to enter and eventually disengage from the host Cell membrane while the secreted RON2 molecules are capped at the posterior pole before being cleaved and released in the medium. By contrast in Cells characterized by low cortex tension and high cortical actin dynamics, Junction capping and entry failure are drastically reduced.ConclusionThis kinematic analysis of pre-invasive and invasive T. gondii tachyzoite behaviors newly highlights that to invade Cells, parasites need to engage their motor with the Junction molecular complex where force is efficiently applied only upon proper anchorage to the host Cell membrane and cortex.
Mary C Beckerle - One of the best experts on this subject based on the ideXlab platform.
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opposing roles of zyxin lpp acta repeats and the lim domain region in Cell Cell adhesion
Journal of Biological Chemistry, 2006Co-Authors: Marc D.h. Hansen, Mary C BeckerleAbstract:Cadherins mediate Cell-Cell adhesion by linking Cell Junctions to actin networks. Although several actin regulatory systems have been implicated in Cell-Cell adhesion, it remains unclear how such systems drive cadherin-actin network formation and how they are regulated to coincide with initiation of adhesion. Previous work implicated VASP in assembly of Cell-Cell Junctions in keratinocytes and the VASP-binding protein zyxin colocalizes with VASP at Cell-Cell Junctions. Here we examine how domains in zyxin and its relative LPP contribute to Cell-Cell Junction assembly. Using a quantitative assay for Cell-Cell adhesion, we demonstrate that zyxin and LPP function to increase the rate of early Cell-Cell Junction assembly through the VASP-binding ActA repeat region. We also identify the LIM region of zyxin and LPP to be a regulatory domain that blocks function of these proteins. Deletion of the LIM domains drives adhesion and increases VASP level in detergent insoluble cadherin-actin. Dominant-negative zyxin/LPP mutants reduce the rate of adhesion, lower VASP levels in detergent-insoluble cadherin-actin networks, and allow for the accumulation of capping protein at Cell-Cell contacts. These data implicate the LIM domains of zyxin and LPP in regulating Cell-Cell Junction assembly through VASP.
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Opposing roles of ZYXIN/LPP ACTA repeats and the LIM domain region in Cell-Cell adhesion
The Journal of biological chemistry, 2006Co-Authors: Marc D.h. Hansen, Mary C BeckerleAbstract:Cadherins mediate Cell-Cell adhesion by linking Cell Junctions to actin networks. Although several actin regulatory systems have been implicated in Cell-Cell adhesion, it remains unclear how such systems drive cadherin-actin network formation and how they are regulated to coincide with initiation of adhesion. Previous work implicated VASP in assembly of Cell-Cell Junctions in keratinocytes and the VASP-binding protein zyxin colocalizes with VASP at Cell-Cell Junctions. Here we examine how domains in zyxin and its relative LPP contribute to Cell-Cell Junction assembly. Using a quantitative assay for Cell-Cell adhesion, we demonstrate that zyxin and LPP function to increase the rate of early Cell-Cell Junction assembly through the VASP-binding ActA repeat region. We also identify the LIM region of zyxin and LPP to be a regulatory domain that blocks function of these proteins. Deletion of the LIM domains drives adhesion and increases VASP level in detergent insoluble cadherin-actin. Dominant-negative zyxin/LPP mutants reduce the rate of adhesion, lower VASP levels in detergent-insoluble cadherin-actin networks, and allow for the accumulation of capping protein at Cell-Cell contacts. These data implicate the LIM domains of zyxin and LPP in regulating Cell-Cell Junction assembly through VASP.