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  1. Article ; Online: Planar cell polarity: coordinating morphogenetic cell behaviors with embryonic polarity.

    Gray, Ryan S / Roszko, Isabelle / Solnica-Krezel, Lilianna

    Developmental cell

    2011  Volume 21, Issue 1, Page(s) 120–133

    Abstract: Planar cell polarization entails establishment of cellular asymmetries within the tissue plane. An evolutionarily conserved planar cell polarity (PCP) signaling system employs intra- and intercellular feedback interactions between its core components, ... ...

    Abstract Planar cell polarization entails establishment of cellular asymmetries within the tissue plane. An evolutionarily conserved planar cell polarity (PCP) signaling system employs intra- and intercellular feedback interactions between its core components, including Frizzled, Van Gogh, Flamingo, Prickle, and Dishevelled, to establish their characteristic asymmetric intracellular distributions and coordinate planar polarity of cell populations. By translating global patterning information into asymmetries of cell membranes and intracellular organelles, PCP signaling coordinates morphogenetic behaviors of individual cells and cell populations with the embryonic polarity. In vertebrates, by polarizing cilia in the node/Kupffer's vesicle, PCP signaling links the anteroposterior to left-right embryonic polarity.
    MeSH term(s) Animals ; Body Patterning ; Cell Polarity ; Cilia/metabolism ; Embryo, Mammalian/cytology ; Embryo, Mammalian/embryology ; Embryo, Mammalian/metabolism ; Frizzled Receptors/metabolism ; Humans ; Microtubule-Organizing Center/metabolism ; Signal Transduction
    Chemical Substances Frizzled Receptors
    Language English
    Publishing date 2011-07-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2011.06.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A dynamic intracellular distribution of Vangl2 accompanies cell polarization during zebrafish gastrulation.

    Roszko, Isabelle / S Sepich, Diane / Jessen, Jason R / Chandrasekhar, Anand / Solnica-Krezel, Lilianna

    Development (Cambridge, England)

    2015  Volume 142, Issue 14, Page(s) 2508–2520

    Abstract: During vertebrate gastrulation, convergence and extension movements elongate embryonic tissues anteroposteriorly and narrow them mediolaterally. Planar cell polarity (PCP) signaling is essential for mediolateral cell elongation underlying these movements, ...

    Abstract During vertebrate gastrulation, convergence and extension movements elongate embryonic tissues anteroposteriorly and narrow them mediolaterally. Planar cell polarity (PCP) signaling is essential for mediolateral cell elongation underlying these movements, but how this polarity arises is poorly understood. We analyzed the elongation, orientation and migration behaviors of lateral mesodermal cells undergoing convergence and extension movements in wild-type zebrafish embryos and mutants for the Wnt/PCP core component Vangl2 (Trilobite). We demonstrate that Vangl2 function is required at the time when cells transition to a highly elongated and mediolaterally aligned body. vangl2 mutant cells fail to undergo this transition and to migrate along a straight path with high net speed towards the dorsal midline. Instead, vangl2 mutant cells exhibit an anterior/animal pole bias in cell body alignment and movement direction, suggesting that PCP signaling promotes effective dorsal migration in part by suppressing anterior/animalward cell polarity and movement. Endogenous Vangl2 protein accumulates at the plasma membrane of mesenchymal converging cells at the time its function is required for mediolaterally polarized cell behavior. Heterochronic cell transplantations demonstrated that Vangl2 cell membrane accumulation is stage dependent and regulated by both intrinsic factors and an extracellular signal, which is distinct from PCP signaling or other gastrulation regulators, including BMP and Nodals. Moreover, mosaic expression of fusion proteins revealed enrichment of Vangl2 at the anterior cell edges of highly mediolaterally elongated cells. These results demonstrate that the dynamic Vangl2 intracellular distribution is coordinated with and necessary for the changes in convergence and extension cell behaviors during gastrulation.
    MeSH term(s) Animals ; Body Patterning ; Cell Lineage ; Cell Membrane/metabolism ; Cell Movement ; Cell Polarity/physiology ; Cytoplasm/metabolism ; Embryo, Nonmammalian/metabolism ; Female ; Gastrula/physiology ; Gastrulation ; Gene Expression Regulation, Developmental ; Membrane Proteins/metabolism ; Membrane Proteins/physiology ; Mesoderm/metabolism ; Mutation ; Neural Plate/metabolism ; Signal Transduction ; Wnt Proteins/metabolism ; Zebrafish ; Zebrafish Proteins/metabolism ; Zebrafish Proteins/physiology
    Chemical Substances Membrane Proteins ; Wnt Proteins ; Zebrafish Proteins ; vangl2 protein, zebrafish
    Language English
    Publishing date 2015-07-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.119032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Regulation of convergence and extension movements during vertebrate gastrulation by the Wnt/PCP pathway.

    Roszko, Isabelle / Sawada, Atsushi / Solnica-Krezel, Lilianna

    Seminars in cell & developmental biology

    2009  Volume 20, Issue 8, Page(s) 986–997

    Abstract: Vertebrate gastrulation entails massive cell movements that establish and shape the germ layers. During gastrulation, the individual cell behaviors are strictly coordinated in time and space by various signaling pathways. These pathways instruct the ... ...

    Abstract Vertebrate gastrulation entails massive cell movements that establish and shape the germ layers. During gastrulation, the individual cell behaviors are strictly coordinated in time and space by various signaling pathways. These pathways instruct the cells about proliferation, shape, fate and migration into proper location. Convergence and extension (C&E) movements during vertebrate gastrulation play a major role in the shaping of the embryonic body. In vertebrates, the Wnt/Planar Cell Polarity (Wnt/PCP) pathway is a key regulator of C&E movements, essential for several polarized cell behaviors, including directed cell migration, and mediolateral and radial cell intercalation. However, the molecular mechanisms underlying the acquisition of Planar Cell Polarity by highly dynamic mesenchymal cells engaged in C&E are still not well understood. Here we review new evidence implicating the Wnt/PCP pathway in specific cell behaviors required for C&E during zebrafish gastrulation, in comparison to other vertebrates. We also discuss findings on the molecular regulation and the interaction of the Wnt/PCP pathway with other signaling pathways during gastrulation movements.
    MeSH term(s) Animals ; Cell Movement ; Cell Polarity ; Gastrulation ; Humans ; Signal Transduction ; Vertebrates/embryology ; Vertebrates/metabolism ; Wnt Proteins/metabolism
    Chemical Substances Wnt Proteins
    Language English
    Publishing date 2009-09-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1312473-0
    ISSN 1096-3634 ; 1084-9521
    ISSN (online) 1096-3634
    ISSN 1084-9521
    DOI 10.1016/j.semcdb.2009.09.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Stem cell growth becomes predominant while neural plate progenitor pool decreases during spinal cord elongation.

    Roszko, Isabelle / Faure, Philippe / Mathis, Luc

    Developmental biology

    2007  Volume 304, Issue 1, Page(s) 232–245

    Abstract: The antero-posterior dispersion of clonally related cells is a prominent feature of axis elongation in vertebrate embryos. Two major models have been proposed: (i) the intercalation of cells by convergent-extension and (ii) the sequential production of ... ...

    Abstract The antero-posterior dispersion of clonally related cells is a prominent feature of axis elongation in vertebrate embryos. Two major models have been proposed: (i) the intercalation of cells by convergent-extension and (ii) the sequential production of the forming axis by stem cells. The relative importance of both of these cell behaviors during the long period of elongation is poorly understood. Here, we use a combination of single cell lineage tracing in the mouse embryo, computer modeling and confocal video-microscopy of GFP labeled cells in the chick embryo to address the mechanisms involved in the antero-posterior dispersion of clones. In the mouse embryo, clones appear as clusters of labeled cells separated by intervals of non-labeled cells. The distribution of intervals between clonally related clusters correlates with a statistical model of a stem cell mode of growth only in the posterior spinal cord. A direct comparison with published data in zebrafish suggests that elongation of the anterior spinal cord involves similar intercalation processes in different vertebrate species. Time-lapse analyses of GFP labeled cells in cultured chick embryos suggest a decrease in the size of the neural progenitor pool and indicate that the dispersion of clones involves ordered changes of neighborhood relationships. We propose that a pre-existing stem zone of growth becomes predominant to form the posterior half of the axis. This temporal change in tissue-level motion is discussed in terms of the clonal and genetic continuities during axis elongation.
    MeSH term(s) Animals ; Body Patterning/physiology ; Cell Lineage/physiology ; Cell Movement/physiology ; Chick Embryo ; Computer Simulation ; Electroporation ; Microscopy, Fluorescence ; Models, Statistical ; Spinal Cord/embryology ; Stem Cells/physiology
    Language English
    Publishing date 2007-04-01
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2006.12.050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Planar Cell Polarity: Coordinating Morphogenetic Cell Behaviors with Embryonic Polarity

    Gray, Ryan S / Roszko, Isabelle / Solnica-Krezel, Lilianna

    Developmental cell. 2011 July 19, v. 21, no. 1

    2011  

    Abstract: Planar cell polarization entails establishment of cellular asymmetries within the tissue plane. An evolutionarily conserved planar cell polarity (PCP) signaling system employs intra- and intercellular feedback interactions between its core components, ... ...

    Abstract Planar cell polarization entails establishment of cellular asymmetries within the tissue plane. An evolutionarily conserved planar cell polarity (PCP) signaling system employs intra- and intercellular feedback interactions between its core components, including Frizzled, Van Gogh, Flamingo, Prickle, and Dishevelled, to establish their characteristic asymmetric intracellular distributions and coordinate planar polarity of cell populations. By translating global patterning information into asymmetries of cell membranes and intracellular organelles, PCP signaling coordinates morphogenetic behaviors of individual cells and cell populations with the embryonic polarity. In vertebrates, by polarizing cilia in the node/Kupffer's vesicle, PCP signaling links the anteroposterior to left-right embryonic polarity.
    Keywords cell membranes ; cell polarity ; cilia ; organelles ; vertebrates
    Language English
    Dates of publication 2011-0719
    Size p. 120-133.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2011.06.011
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  6. Article ; Online: Gpr125 modulates Dishevelled distribution and planar cell polarity signaling.

    Li, Xin / Roszko, Isabelle / Sepich, Diane S / Ni, Mingwei / Hamm, Heidi E / Marlow, Florence L / Solnica-Krezel, Lilianna

    Development (Cambridge, England)

    2013  Volume 140, Issue 14, Page(s) 3028–3039

    Abstract: During vertebrate gastrulation, Wnt/planar cell polarity (PCP) signaling orchestrates polarized cell behaviors underlying convergence and extension (C&E) movements to narrow embryonic tissues mediolaterally and lengthen them anteroposteriorly. Here, we ... ...

    Abstract During vertebrate gastrulation, Wnt/planar cell polarity (PCP) signaling orchestrates polarized cell behaviors underlying convergence and extension (C&E) movements to narrow embryonic tissues mediolaterally and lengthen them anteroposteriorly. Here, we have identified Gpr125, an adhesion G protein-coupled receptor, as a novel modulator of the Wnt/PCP signaling system. Excess Gpr125 impaired C&E movements and the underlying cell and molecular polarities. Reduced Gpr125 function exacerbated the C&E and facial branchiomotor neuron (FBMN) migration defects of embryos with reduced Wnt/PCP signaling. At the molecular level, Gpr125 recruited Dishevelled to the cell membrane, a prerequisite for Wnt/PCP activation. Moreover, Gpr125 and Dvl mutually clustered one another to form discrete membrane subdomains, and the Gpr125 intracellular domain directly interacted with Dvl in pull-down assays. Intriguingly, Dvl and Gpr125 were able to recruit a subset of PCP components into membrane subdomains, suggesting that Gpr125 may modulate the composition of Wnt/PCP membrane complexes. Our study reveals a role for Gpr125 in PCP-mediated processes and provides mechanistic insight into Wnt/PCP signaling.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Cell Movement ; Cell Polarity ; Dishevelled Proteins ; Embryo, Nonmammalian/cytology ; Embryo, Nonmammalian/metabolism ; Mutation ; Phosphoproteins/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Wings, Animal/cytology ; Wings, Animal/embryology ; Wnt Signaling Pathway ; Zebrafish/embryology ; Zebrafish/metabolism ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
    Chemical Substances Adaptor Proteins, Signal Transducing ; Dishevelled Proteins ; Phosphoproteins ; Receptors, G-Protein-Coupled ; Zebrafish Proteins ; adgra3 protein, zebrafish
    Language English
    Publishing date 2013-07-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.094839
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease.

    Kundishora, Adam J / Peters, Samuel T / Pinard, Amélie / Duran, Daniel / Panchagnula, Shreyas / Barak, Tanyeri / Miyagishima, Danielle F / Dong, Weilai / Smith, Hannah / Ocken, Jack / Dunbar, Ashley / Nelson-Williams, Carol / Haider, Shozeb / Walker, Rebecca L / Li, Boyang / Zhao, Hongyu / Thumkeo, Dean / Marlier, Arnaud / Duy, Phan Q /
    Diab, Nicholas S / Reeves, Benjamin C / Robert, Stephanie M / Sujijantarat, Nanthiya / Stratman, Amber N / Chen, Yi-Hsien / Zhao, Shujuan / Roszko, Isabelle / Lu, Qiongshi / Zhang, Bo / Mane, Shrikant / Castaldi, Christopher / López-Giráldez, Francesc / Knight, James R / Bamshad, Michael J / Nickerson, Deborah A / Geschwind, Daniel H / Chen, Shih-Shan Lang / Storm, Phillip B / Diluna, Michael L / Matouk, Charles C / Orbach, Darren B / Alper, Seth L / Smith, Edward R / Lifton, Richard P / Gunel, Murat / Milewicz, Dianna M / Jin, Sheng Chih / Kahle, Kristopher T

    JAMA neurology

    2021  Volume 78, Issue 8, Page(s) 993–1003

    Abstract: Importance: Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a ... ...

    Abstract Importance: Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals.
    Objective: To assess whether ultrarare de novo and rare, damaging transmitted variants with large effect sizes are associated with MMD risk.
    Design, setting, and participants: A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records from US hospitals spanning a range of 1 month to 1.5 years were reviewed for phenotyping. Exomes from a larger validation cohort were analyzed to identify additional rare, large-effect variants in the top candidate gene. Participants included patients with MMD and, when available, their parents. All participants who met criteria and were presented with the option to join the study agreed to do so; none were excluded. Twenty-four probands (22 trios and 2 singletons) composed the discovery cohort, and 84 probands (29 trios and 55 singletons) composed the validation cohort.
    Main outcomes and measures: Gene variants were identified and filtered using stringent criteria. Enrichment and case-control tests assessed gene-level variant burden. In silico modeling estimated the probability of variant association with protein structure. Integrative genomics assessed expression patterns of MMD risk genes derived from single-cell RNA sequencing data of human and mouse brain tissue.
    Results: Of the 24 patients in the discovery cohort, 14 (58.3%) were men and 18 (75.0%) were of European ancestry. Three of 24 discovery cohort probands contained 2 do novo (1-tailed Poisson P = 1.1 × 10-6) and 1 rare, transmitted damaging variant (12.5% of cases) in DIAPH1 (mammalian diaphanous-1), a key regulator of actin remodeling in vascular cells and platelets. Four additional ultrarare damaging heterozygous DIAPH1 variants (3 unphased) were identified in 3 other patients in an 84-proband validation cohort (73.8% female, 77.4% European). All 6 patients were non-East Asian. Compound heterozygous variants were identified in ena/vasodilator-stimulated phosphoproteinlike protein EVL, a mammalian diaphanous-1 interactor that regulates actin polymerization. DIAPH1 and EVL mutant probands had severe, bilateral MMD associated with transfusion-dependent thrombocytopenia. DIAPH1 and other MMD risk genes are enriched in mural cells of midgestational human brain. The DIAPH1 coexpression network converges in vascular cell actin cytoskeleton regulatory pathways.
    Conclusions and relevance: These findings provide the largest collection to date of non-East Asian individuals with sporadic MMD harboring pathogenic variants in the same gene. The results suggest that DIAPH1 is a novel MMD risk gene and impaired vascular cell actin remodeling in MMD pathogenesis, with diagnostic and therapeutic ramifications.
    MeSH term(s) Adult ; Age of Onset ; Cell Adhesion Molecules/genetics ; Child ; Child, Preschool ; Cohort Studies ; Computer Simulation ; Exome/genetics ; Female ; Formins/genetics ; Genetic Variation ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Moyamoya Disease/diagnostic imaging ; Moyamoya Disease/genetics ; Phenotype ; Sequence Analysis, RNA ; White People ; Exome Sequencing
    Chemical Substances Cell Adhesion Molecules ; DIAPH1 protein, human ; EVL protein, human ; Formins
    Language English
    Publishing date 2021-06-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2702023-X
    ISSN 2168-6157 ; 2168-6149
    ISSN (online) 2168-6157
    ISSN 2168-6149
    DOI 10.1001/jamaneurol.2021.1681
    Database MEDical Literature Analysis and Retrieval System OnLINE

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