Cellular Adhesion in Development and Disease

 
 
Academic Press
  • 1. Auflage
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  • erschienen am 27. Februar 2015
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  • 536 Seiten
 
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978-0-12-407889-5 (ISBN)
 

Cell adhesion is a fundamental determinant of embryonic development and organogenesis. Cellular Adhesion in Development and Disease, volume 112 in Current Topics in Developmental Biology, comprehensively surveys current developments in understanding how adhesion systems affect organismal development. Topics covered include nectins, nectin-like molecules, and afadin in development; cadherin adhesion, signaling, and morphogenesis; endothelial cell junctions; epidermal development and barrier formation; and more.


  • This book surveys current understanding of how adhesion systems affect organismal development
0070-2153
  • Englisch
  • Saint Louis
  • |
  • USA
Elsevier Science
  • 19,20 MB
978-0-12-407889-5 (9780124078895)
0124078893 (0124078893)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Cellular Adhesion in Development and Disease
  • Copyright
  • Contents
  • Contributors
  • Preface
  • Chapter 1: How Adhesion Forms the Early Mammalian Embryo
  • 1. The Mouse Preimplantation Embryo as a Model of Adhesion in Mammalian Development
  • 1.1. Adhesion molecules in the preimplantation mouse embryo
  • 2. Adhesion Regulates Cell Shape
  • 3. Adhesion Controls Cell Polarity
  • 4. Adhesion Determines Cell Fate
  • 5. Emerging Technologies to Study Adhesion
  • 6. Questions for the Future
  • References
  • Chapter 2: Regulation of Cell Adhesion and Cell Sorting at Embryonic Boundaries
  • 1. Introduction
  • 2. A Short History of Tissue Separation
  • 2.1. Cell sorting and ``affinities´´
  • 2.2. Compartments
  • 2.3. The differential adhesion hypothesis
  • 2.4. Differential CAM expression
  • 2.5. Contact inhibition
  • 2.6. Differential interfacial tension
  • 2.7. Direct investigation of basic properties: Embryonic boundaries are not stable physical structures, but the dynamic p...
  • 3. Adhesion and Contractility of Embryonic Tissues
  • 3.1. Methodology
  • 3.2. Germ layers
  • 3.3. Notochord-presomitic mesoderm boundary
  • 3.4. Somite and hindbrain segmentation
  • 3.5. Drosophila tissues
  • 3.6. Boundaries reflect abrupt discontinuities in tissue properties
  • 3.6.1. Principles of regulation of cell adhesion
  • 4. Molecular Base of Separation in Vertebrates: Ephrins-Eph Signaling
  • 5. Homophilic Contact Molecules at Embryonic Boundaries
  • 5.1. Immunoglobulin CAMs, Echinoid
  • 5.2. Leucine-rich repeat proteins, FLRT3
  • 5.3. Protocadherins, PAPC
  • 5.4. EpCAM, inducer of tissue mixing
  • 6. Regulation of Tension and Adhesion by Contact Cues
  • 6.1. The action of homophilic regulators
  • 6.2. Putting pro- and antiadhesive activities together
  • 6.2.1. Note about complexity and redundancy
  • 6.2.2. After separation: Relationship between separation and epithelization
  • 7. Conclusions
  • Acknowledgments
  • References
  • Chapter 3: Active Tension: The Role of Cadherin Adhesion and Signaling in Generating Junctional Contractility
  • 1. Introduction
  • 2. The Contractile Apparatus: Actomyosin
  • 2.1. The role of cadherin signaling in myosin II regulation
  • 2.2. F-actin mediates the association of myosin motors with cadherin adhesion
  • 3. Cadherins and Biogenesis of the Junctional Actin Cytoskeleton
  • 3.1. The dynamic junctional actin cytoskeleton
  • 3.2. Actin assembly
  • 3.3. Actin filament stability and junctional contractility
  • 4. Regulation of Cortical Signaling by Cadherin Adhesion
  • 4.1. Rho signaling and morphogenesis
  • 4.2. Rho and cadherin biology
  • 4.3. Focusing Rho signaling at cell-cell junctions
  • 4.4. ECT2
  • 4.5. p190 RhoGAP
  • 4.6. Coordinating GEF and GAP activity
  • 4.7. Other mechanisms
  • 4.8. Localizing ROCK to junctions
  • 5. Closing Comments
  • Acknowledgments
  • References
  • Chapter 4: Integration of Cell-Cell Adhesion and Contractile Actomyosin Activity During Morphogenesis
  • 1. Introduction
  • 2. Molecular Interplay Between Cadherin Adhesion Receptors and the Actomyosin Cytoskeleton
  • 2.1. The Cadherin complex
  • 2.2. The Cadherin-actin link
  • 2.3. Other apical adhesion and homophilic receptors acting on the cytoskeleton
  • 2.3.1. Nectins/Echinoid and the actin cytoskeleton
  • 2.3.2. Crumbs and the organization of actomyosin
  • 3. Integration of Adhesion and Contractility During Morphogenesis
  • 3.1. Medial myosin during mesoderm invagination in Drosophila
  • 3.2. Myosin flows during gastrulation in C. elegans
  • 3.3. Planar polarized myosin and myosin flows during germband extension in Drosophila
  • 3.4. Medial myosin and a myosin cable during dorsal closure in Drosophila
  • 3.5. An actomyosin cable during tube morphogenesis in Drosophila
  • 4. Role of Tension-Sensing in Adherens Junctions in Regulating Cell Shape and Morphogenesis
  • 4.1. Tension-sensing roles for a-catenin and vinculin in Adherens Junctions
  • 4.2. Using tension sensors to study contractility and tension during morphogenesis
  • 5. Summary
  • Acknowledgments
  • References
  • Chapter 5: Nuclear Signaling from Cadherin Adhesion Complexes
  • 1. ß-Catenin, a Dual-Function Adhesion/Transcriptional Coactivator Protein
  • 2. Cadherins as Stoichiometric Inhibitors of Wnt/ß-Catenin Signaling
  • 3. The Cadherin-Catenin Complex as Both a Potentiator and an Attenuator of Wnt/ß-Catenin Signaling
  • 3.1. Cadherin-based adhesion and destruction complex activity
  • 3.2. Cadherins as facilitators of Wnt/ß-catenin signaling
  • 4. Cadherin Signaling and Stem Cell Behavior
  • 5. ß-Catenin ``Release´´ from Cortical Endosomes and Nuclear Signaling
  • 6. The Other Catenins
  • 7. Nuclear Signaling Functions of the Actin-Binding Protein, a-Catenin
  • 8. Cadherin Nuclear Signaling via RTKs
  • 8.1. Cadherin-mediated inhibition of diverse RTKs
  • 8.2. ß-Catenin as a key target of RTKs and other membrane-activated kinases
  • 9. Cadherin Nuclear Signaling by Small GTPases and NF?B
  • 10. Cadherin Nuclear Signaling via Proteolysis
  • 11. Protocadherin Signaling to the Nucleus
  • 12. Atypical Cadherin Nuclear Signaling
  • 13. Cadherin Nuclear Signaling via the Hippo Pathway
  • 14. Stem Cell Maintenance via Cadherin Nuclear Signaling
  • 15. Desmosomal Cadherin Nuclear Signaling
  • 16. Conclusions
  • Acknowledgments
  • References
  • Chapter 6: Nectins and Nectin-Like Molecules in Development and Disease
  • 1. Introduction
  • 2. Physical Properties
  • 2.1. Molecular properties
  • 2.2. Binding properties of the extracellular regions
  • 2.3. Binding properties of the intracellular regions
  • 3. Functional Properties
  • 3.1. Cell proliferation
  • 3.2. Cell differentiation
  • 3.3. Cell movement
  • 3.4. Cell adhesion
  • 4. Development
  • 4.1. Spermatogenesis
  • 4.2. Eye development
  • 4.3. Inner ear development
  • 4.4. Tooth development
  • 4.5. Cerebral cortex development
  • 4.6. Axon guidance
  • 4.7. Synapse formation
  • 4.8. Myelination
  • 5. Diseases
  • 5.1. Viral infection
  • 5.2. Ectodermal dysplasia
  • 5.3. Alzheimer´s disease
  • 5.4. Neurodevelopmental disorder
  • 5.5. Stress-related mental disorders
  • 5.6. Cancer
  • 6. Conclusions and Perspectives
  • Acknowledgments
  • References
  • Chapter 7: Anchors and Signals: The Diverse Roles of Integrins in Development
  • 1. Introduction
  • 1.1. Developmental biology: Signaling and mechanics
  • 1.2. The identification of integrins and their exploration in cell culture and whole animal models
  • 1.3. Integrins: Signaling and mechanics
  • 2. Integrins in Choices of Life and Death: Animal Lethal, not Always Cell Lethal
  • 3. Integrins and Cell Fate Choices
  • 3.1. Mechanotransduction of matrix properties by stem cells
  • 3.2. Stem cells in vivo: Niche integrity via anchorage
  • 3.3. Induction in vivo: Beyond the niche
  • 4. Integrins in Single and Collective Cell Migration: Beyond the Fibroblast Model
  • 4.1. Integrins powering and modulating cell movement, cell autonomously, and nonautonomously
  • 4.2. Integrin-independent cell movement in vivo
  • 5. Building Tissues and Organs: Snags and Anchors
  • 6. Integrins in Epithelia: Cell Polarity and Division Orientation
  • 7. Outlook
  • Acknowledgments
  • References
  • Chapter 8: Epithelial-Mesenchymal Transitions: From Cell Plasticity to Concept Elasticity
  • 1. Back to the Origins: Defining EMT
  • 2. EMT is a Morphogenic Developmental Process, or is it?
  • 3. Controlling EMT or Being Controlled by EMT
  • 4. Revisiting EMT in Cancer
  • 5. Are Cancer Cells Reactivating an Embryonic Process or Barely Surviving?
  • 6. EMT With or Without Cadherins: A Cancer Metastable Phenotype
  • 7. Conclusion
  • References
  • Chapter 9: Embryonic Cell-Cell Adhesion: A Key Player in Collective Neural Crest Migration
  • 1. Introduction
  • 1.1. Neural crest cells
  • 1.1.1. Neural crest formation
  • 1.1.2. Neural crest cell migration
  • 1.2. Front-rear planar cell polarity
  • 1.3. Cell-cell adhesion during migration
  • 2. Cell-Cell Adhesion During Neural Crest Cell Directional Collective Migration
  • 2.1. Epithelial-to-mesenchymal transition
  • 2.2. Contact inhibition of locomotion
  • 2.3. Chemotaxis
  • 2.4. Coattraction
  • 2.5. Cell-cell adhesion molecule turnover
  • 3. Concluding Remarks
  • Acknowledgments
  • References
  • Chapter 10: VE-cadherin in Vascular Development: A Coordinator of Cell Signaling and Tissue Morphogenesis
  • 1. Vascular Cell Adhesion
  • 2. VE-cadherin as a Physical Adaptor
  • 3. Modulation of VE-cadherin by Kinases, Phosphatases, and Small GTPases
  • 4. VE-cadherin in Vessel Development and Morphogenesis
  • 5. VE-cadherin and Vascular Signaling During Angiogenesis and Morphogenesis
  • 5.1. VEGF signaling, FGF signaling, and angiogenic VE-cadherin
  • 5.2. Notch signaling and VE-cadherin in angiogenesis
  • 5.3. Angiopoietin-Tie signaling and junctional regulation
  • 5.4. TGF-ß-Smad signaling and VE-cadherin
  • 5.5. VE-cadherin and the potential for regulation of other signaling events
  • 6. Conclusions
  • Acknowledgements
  • References
  • Chapter 11: Adhesion in Mammary Development: Novel Roles for E-Cadherin in Individual and Collective Cell Migration
  • 1. Introduction
  • 2. Cell-Cell Adhesion in Mammary Development: The Major Players
  • 2.1. From simple to stratified: Transitions in adhesion during morphogenesis
  • 2.2. Adherens junctions
  • 2.2.1. Early requirement for E-cadherin
  • 2.2.2. Strategies for genetic analysis in the postnatal mammary gland
  • 2.2.3. Postnatal analysis of E-cadherin function in the mammary gland
  • 2.2.4. P-cadherin
  • 2.2.5. Catenins
  • 2.3. Desmosomes
  • 3. Cell-Cell Adhesion in Breast Cancer
  • 3.1. E-cadherin: An invasion suppressor?
  • 3.2. Cadherin switching
  • 3.3. Rethinking the epithelial-to-mesenchymal transition
  • 3.4. ``Unexpected´´ roles for E-cadherin
  • 4. Can a Migratory Single Cell or Cell Cluster Be ``Epithelial´´?
  • 4.1. Dissemination: A transition in the substrate for migration
  • 4.2. Balancing cell-cell and cell-matrix adhesion
  • 4.3. Novel functions for classic molecules: Next steps in adhesion biology
  • Acknowledgments
  • References
  • Chapter 12: Cell Adhesion in Epidermal Development and Barrier Formation
  • 1. Introduction
  • 2. Development of the Stratified Epidermis
  • 2.1. Periderm function-An antiadhesive?
  • 3. Adherens Junctions
  • 3.1. Epidermal adhesion defects upon loss of AJ proteins
  • 3.2. AJs link actin to the cell cortex
  • 3.3. AJs sense and respond to tension
  • 3.4. AJs in hair follicle morphogenesis
  • 3.5. Noncanonical roles for catenins
  • 4. Desmosomes
  • 4.1. Desmosomal proteins in epidermal integrity and disease
  • 4.1.1. Desmoplakin
  • 4.1.2. Plakoglobin
  • 4.1.3. Desmosomal cadherins
  • 4.1.4. Pemphigus
  • 4.2. Desmosomes in hair follicle morphogenesis
  • 4.3. Noncanonical roles for desmosomal proteins
  • 4.3.1. Microtubule organization
  • 4.3.2. Actin organization
  • 4.3.3. Signaling/transcription
  • 5. Tight Junctions
  • 5.1. Tight junctions in the epidermis
  • 5.2. Tight junctions in epidermal development and barrier formation
  • 5.3. Tight junctions in disease
  • 6. Junctional Crosstalk in Epidermal Function
  • References
  • Chapter 13: Cadherin-Based Transsynaptic Networks in Establishing and Modifying Neural Connectivity
  • 1. Introduction
  • 2. The Cadherin Superfamily
  • 2.1. Classification and structure
  • 2.2. Cadherin localization in the central nervous system
  • 3. Functional Units of Adhesion and Signaling: Intra- and Inter-CAM Family Cross talk (Table1)
  • 4. Developmental Phases of Circuit Assembly: Evolving Roles of the Cadherin-Based Adhesive Network
  • 4.1. Neurogenesis and migration
  • 4.2. Axon outgrowth and targeting
  • 4.3. Elaboration of dendrites, arborization, and self-avoidance
  • 4.4. Synaptogenesis, dendritic spine formation, and synaptic plasticity in developing neurons
  • 5. Beyond Development: What Does the Cadherin-Catenin Transsynaptic Network Contribute to Brain Function Throughout Life?
  • 5.1. Cadherins become dispensible for maintaining hippocampal connectivity but regulate dynamic aspects of synaptic funct...
  • 5.2. Postnatal deletion of N-cadherin may alter the balance of excitation and inhibition
  • 5.3. Deficits in cognitive flexibility in adult cadherin-mutant mice
  • 6. Cadherin-Based Transsynaptic Networks in Pathophysiology of Brain Circuits
  • 6.1. Neurodevelopmental disorders
  • 6.2. Seizure/epilepsy
  • 6.3. CNS lesions, neuropathic pain, astrogliosis, and remyelination
  • 6.4. Alzheimer´s disease
  • 7. Conclusions
  • Acknowledgments
  • References
  • Chapter 14: Cell-Cell Interactions Driving Kidney Morphogenesis
  • 1. Introduction
  • 2. Cell-Cell Interactions Within the Developing Ureteric Epithelium
  • 3. The Nephrogenic Niche-Balancing Self-Renewal and Differentiation
  • 4. Mediators of CM Integrity, Identity, and Morphology
  • 5. Differential Cell-Cell Adhesion in Nephron Formation, Fusion, Patterning, and Segmentation
  • 6. The Adhesion-Cytoskeleton-Signaling Axis in Kidney Tubulogenesis
  • 7. Formation of the Glomerular Filter
  • 8. In Vitro Self-Organization Generates Kidney Organoids
  • 9. Self-Organization in Directed Differentiation to Kidney
  • 10. Application of Cell-Cell and Cell-Matrix Interactions Kidney Tissue Engineering
  • 11. Conclusion
  • Acknowledgments
  • References
  • Index
  • Color Plate
Chapter One

How Adhesion Forms the Early Mammalian Embryo


Melanie D. White; Nicolas Plachta1    European Molecular Biology Laboratory (EMBL) Australia, Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia
1 Corresponding author: email address: nicolas.plachta@emblaustralia.org

Abstract


The early mouse embryo is an excellent system to study how a small group of initially rounded cells start to change shape and establish the first forms of adhesion-based cell-cell interactions in mammals in vivo. In addition to its critical role in the structural integrity of the embryo, we discuss here how adhesion is important to regulate cell polarity and cell fate. Recent evidence suggests that adherens junctions participate in signaling pathways by localizing key proteins to subcellular microdomains. E-cadherin has been identified as the main player required for the establishment of adhesion but other mechanisms involving additional proteins or physical forces acting in the embryo may also contribute. Application of new technologies that enable high-resolution quantitative imaging of adhesion protein dynamics and measurements of biomechanical forces will provide a greater understanding of how adhesion patterns the early mammalian embryo.

Keywords

Adhesion

Preimplantation development

Mouse embryo

E-cadherin

Pluripotent cell

Blastocyst

1 The Mouse Preimplantation Embryo as a Model of Adhesion in Mammalian Development


Most research on adhesion has been performed on cells in tissue culture due to their availability and ease of manipulation. However, it is only during true cellular differentiation within an embryo that the contribution of adhesion to development can be examined directly. The mouse preimplantation embryo provides an ideal system to study adhesion mechanisms that are based exclusively on cell-cell interactions. A glycoprotein membrane, the zona pellucida, encloses the preimplantation embryo so cell-cell adhesion can be studied in the complete absence of extracellular matrix interactions.

Preimplantation development naturally occurs within the oviduct, but it can be recapitulated in vitro without adversely affecting the developmental potential of embryos (Summers & Biggers, 2003). Mouse embryos can be easily removed from the maternal oviducts and cultured in simple media conditions. Under these ex utero conditions, the embryos develop almost as rapidly as they do in utero and if transferred back to the uterus they can implant and continue developing to produce viable offspring.

During the first 2 days of development, the fertilized mouse egg undergoes three cleavage divisions to produce an 8-cell embryo (Fig. 1A). At this stage, the cells are round and visibly indistinguishable. The first major cell morphological changes begin as the 8-cell embryo undergoes compaction. Concomitant with a rise in intercellular adhesion, the cells flatten their membranes against each other, maximizing contact and forming a highly packed mass. This process of increased adhesion and embryo compaction occurs ubiquitously during preimplantation development in different mammalian species and is an absolute requirement for embryo viability. This process is very similar in mouse and humans, making the preimplantation mouse embryo an ideal model to study the role of adhesion in cell shape, position, and fate in early mammalian development. In addition, the cells of the mouse embryo are relatively large, facilitating imaging of subcellular processes. Furthermore, there are many available genetic tools that are applicable in the mouse for manipulation of proteins of interest. Pronuclear microinjection of mRNA or DNA is a well-established technique for expression of exogenous proteins and mouse embryos are resilient enough to withstand this process with high efficiency (Fig. 1B). Moreover, thousands of genetically modified animals are now available carrying targeted endogenous genes or expressing various transgenic constructs.

Figure 1 Imaging preimplantation development in the mouse embryo. (A) DIC images showing development of mouse embryo from 1-cell to blastocyst stage. (B) Microinjection of mRNA or DNA into the pronucleus allows visualization of proteins of interest throughout preimplantation development. In the example shown, the membrane is labeled with mCherry and the nucleus is labeled with H2B-GFP. ICM, inner cell mass; TE, trophectoderm.

1.1 Adhesion molecules in the preimplantation mouse embryo


Early studies identified a critical role for calcium-dependent adhesion in embryo compaction, subsequent spatial segregation of the inner cell mass (ICM) and formation of the first differentiated tissue, the trophectoderm (Fleming, Sheth, & Fesenko, 2001). Interfering with adhesion by chelating calcium ions or using antibodies targeting a cell surface glycoprotein decompacted embryos and prevented blastocyst formation (Ducibella & Anderson, 1975; Wales, 1970; Whitten, 1971). In 1981, this cell surface glycoprotein was identified as uvomorulin, now more commonly known as E-cadherin (Hyafil, Babinet, & Jacob, 1981).

Although usually expressed in epithelial cell layers, E-cadherin is also expressed from the very early stages of development. It is initially maternally derived in the oocyte and at the 2-cell stage, de novo E-cadherin zygotic synthesis starts (Vestweber, Gossler, Boller, & Kemler, 1987). Embryos lacking zygotic E-cadherin are preimplantation lethal. They do undergo compaction due to residual maternal E-cadherin but fail to form a blastocyst (Larue, Ohsugi, Hirchenhain, & Kemler, 1994). Using siRNAs to knockdown E-cadherin expression in just half of the embryo prevents those cells from integrating into the compacting embryo (Fig. 2) (Fierro-Gonzalez, White, Silva, & Plachta, 2013). Embryos lacking both maternal and zygotic E-cadherin are unable to compact or form a blastocyst and they appear as loose aggregates of cells (Stephenson, Yamanaka, & Rossant, 2010). Deleting maternal E-cadherin alone delays compaction until the late morula stage but embryos then develop normally due to zygotic E-cadherin expression (De Vries et al., 2004). Adhesion does not develop until the late morula stage in these embryos indicating that although E-cadherin and its binding partners are expressed (Ohsugi et al., 1996; Sefton, Johnson, & Clayton, 1992; Vestweber et al., 1987), they are not required to form functional adhesion complexes at very early stages.

Figure 2 E-cadherin is required for cell-cell adhesion and embryo compaction. (A) Microinjection of one cell at the 2-cell stage results in an embryo expressing a control siRNA and a membrane-Cherry marker in half of its cells. The transgenic cells have normal morphology and integrate into the compacting embryo mass. (B) An siRNA targeting E-cadherin reduces cell-cell adhesion in the transgenic half of the embryo. The nontransgenic cells compact normally but the E-cadherin knockdown cells are very spherical and do not integrate into the embryo mass. (C) Treating the embryo with the DECMA-1 E-cadherin function-blocking antibody reduces adhesion and causes all cells to become very spherical. The embryo does not compact. Scale bar = 10 µm.

E-cadherin is uniformly distributed in the cell membrane until the 8-cell stage when PKC-a-mediated phosphorylation of ß-catenin, a key protein regulating E-cadherin intracellular signaling, is thought to activate the compaction process (Fig. 3; Pauken & Capco, 1999). Compaction can be blocked by inhibition of PKC-a and induced early at the 2- and 4-cell stages by PKC-a activation (Ohsugi, Ohsawa, & Semba, 1993; Winkel, Ferguson, Takeichi, & Nuccitelli, 1990). E-cadherin accumulates basolaterally, forming adherens junctions between cells and connecting to the actin cytoskeleton via catenin proteins (Ozawa, Ringwald, & Kemler, 1990). As adhesion initiates, the actin cytoskeleton is reorganized to define the orientation of the first cellular polarity in the embryo (Stephenson et al., 2010).

Figure 3 E-cadherin localization changes during preimplantation development. E-cadherin is distributed throughout the membrane until the late 8-cell stage. Then, it begins to accumulate in cell-cell junctions and is predominantly localized to basolateral regions by the 16-cell stage.

After compaction has occurred, tight junctions begin to assemble at apicolateral cell-cell junctions in a process that requires prior activation of E-cadherin-mediated adhesion (Fleming, McConnell, Johnson, & Stevenson, 1989; Ohsugi, Larue, Schwarz, & Kemler, 1997). The timing of tight junction formation is tightly regulated by staggered expression of the constituent proteins from the 8- to 32-cell stage (Sheth et al., 1997). E-cadherin-mediated adhesion may also stabilize tight junction proteins, preventing their turnover once they are assembled at the membrane (Javed, Fleming, Hay, & Citi, 1993). The close intercellular adhesion at tight junctions then forms a permeability seal between...

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