E-Cadherin Regulates Neural Stem Cell Self-Renewal

Karpowicz, Phillip; Willaime‐Morawek, Sandrine; Balenci, Laurent; DeVeale, Brian; Inoue, Tomoyuki; Kooy, Derek van der

doi:10.1523/jneurosci.0037-09.2009

Cited by 95 publications

(94 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This possibility is supported by the finding that the loss of cadherin function, which disrupts cellcell junctions within germ line stem cells, causes the subsequent loss of ovarian and testicular stem cells in Drosophila (Song et al, 2002) and mice (Karpowicz et al, 2009). However, these mechanical cues must be integrated with other chemical signals, such as growth factors (e.g.…”

Section: Cytoskeletal Tension As a Fundamental Bioregulatormentioning

confidence: 92%

Mechanical control of tissue and organ development

2010

View full text Add to dashboard Cite

Many genes and molecules that drive tissue patterning during organogenesis and tissue regeneration have been discovered. Yet, we still lack a full understanding of how these chemical cues induce the formation of living tissues with their unique shapes and material properties. Here, we review work based on the convergence of physics, engineering and biology that suggests that mechanical forces generated by living cells are as crucial as genes and chemical signals for the control of embryological development, morphogenesis and tissue patterning. Key words: Cytoskeleton, Mechanical signaling, Morphogenesis, Pattern formation, Tension IntroductionWe now know many genes, morphogens and signaling molecules that govern tissue genesis. However, we do not fully understand how these chemical cues drive the formation of living tissues and organs with specialized forms and unique physical properties (e.g. rigidity, elastic recoil or viscoelasticity) required to pump blood, withstand repetitive movements or lift our bodies up against the force of gravity. A century ago, much of developmental control was explained in mechanical terms. In his classic treatise On Growth and Form, D'Arcy Thompson described how patterns are "diagrams of underlying forces" (Thompson, 1917). This is because a change in the three-dimensional (3D) shape of any structure, including living cells and tissues, must, at some level, result from the action of a force acting on a mass. Although this view was pushed aside by the advance of molecular biology, the relationship between physicality and developmental control is now coming into focus once again as a result of powerful new alliances between biologists, geneticists, engineers and physicists. This interdisciplinary approach has led to the discovery of fundamental links between mechanical forces, molecular biochemistry, gene expression and tissue patterning that drive embryogenesis and play a central role in morphogenesis and tissue maintenance throughout the life of an organism.In this article, we highlight some of the recent advances in this emerging field of mechanical biology. In particular, we focus on the role of mechanical forces that are generated in the contractile actin cytoskeleton of living cells and that act on the adhesions of these cells to neighboring cells and to the extracellular matrix (ECM). We describe how both traction forces exerted locally by single cells and more generalized forces (e.g. fluid shear, hydrostatic pressure) resulting from tension generated within the cytoskeletons of large groups of cells in tissues and organs are central to the control of tissue pattern formation during virtually all stages of embryogenesis.We also explore how mechanical signals are converted into changes in intracellular biochemistry and gene expression so that they influence fundamental mechanisms of cell fate determination and morphogenetic control that are also controlled by genes, soluble morphogens and chemical factors. Mechanical forces in early developmentThe shaping of the living embryo...

show abstract

Section: Cytoskeletal Tension As a Fundamental Bioregulatormentioning

confidence: 92%

Mechanical control of tissue and organ development

2010

View full text Add to dashboard Cite

show abstract

“…Adherent junction molecules, such as E-cadherin, connexin, and occludin, have been known to influence the migration of stem cells as well as proliferation [39]. The loss of cell-cell junctions elicited increase in migration of stem cells, including ESCs and adult stem cells [40][41][42][43], suggesting that the cell junction molecules are essential for regulation of stem cell migration.…”

Section: Resultsmentioning

confidence: 99%

cAMP Promotes Cell Migration Through Cell Junctional Complex Dynamics and Actin Cytoskeleton Remodeling: Implications in Skin Wound Healing

Kim

Ryu

Park

et al. 2015

Stem Cells and Development

View full text Add to dashboard Cite

Stem cells have attracted great interest for their therapeutic capacity in tissue regeneration. Cyclic adenosine 3¢,5¢-monophosphate (cAMP), existing in high concentration at wound sites, mediated various signaling pathways such as cytoskeleton dynamics, cell adhesion, and cell migration in stem cells, which suggest the critical roles of cAMP in the wound healing process through functional regulation of stem cells. However, the mechanisms behind the effect of cAMP on mouse embryonic stem cell (mESC) motility and its roles on skin wound healing remain to be fully elucidated. In the present study, 8-Bromo cAMP-treated mESCs showed significant wound closure and improved neovascularization. Moreover, 8-Bromo cAMP stimulated mESC migration into the wound bed. 8-Bromo cAMP also increased ESC motility in in vitro migration assay. 8-Bromo cAMP induced myosin light chain phosphorylation through Rac1 and Cdc42 signaling, which were involved in 8-Bromo cAMP-induced decrease in expression of junction proteins (connexin 43, E-cadherin, and occludin) at the plasma membrane. Subsequently, 8-Bromo cAMP induced the disruption of cell junctions (including gap junctions, adherens junctions, and tight junctions), which reduced the function of the gap junctions and cell adhesion. In addition, 8-Bromo cAMP-induced Rac1 and Cdc42 activation increased Arp3, TOCA, PAK, and N-WASP expression, but decreased cofilin phosphorylation level, which elicited actin cytoskeleton remodeling. In contrast to the control, 8-Bromo cAMP evoked a substantial migration of cells into the denuded area, which was blocked by the small interfering RNAs of the signaling pathway-related molecules or by inhibitors. In conclusion, cAMP enhanced the migration of mESCs through effective coordination of junctional disruption and actin cytoskeleton remodeling, which increased the wound healing capacity of ESCs.

show abstract

“…One possibility could be that additional non-characterized factors might be present in vivo and completely repress adult RSC proliferation. An alternative explanation might be that, in vivo, RSCs are part of an epithelium harboring numerous cell-cell contacts, which are important in regulating the proliferation of stem cells in several systems and may participate in the induction of adult RSC quiescence [51][52][53].…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells

et al. 2013

View full text Add to dashboard Cite

Rare retinal stem cells (RSCs) within the ciliary epithelium at the retinal margin of the adult mouse and human eyes can divide in vitro in the absence of growth factors to generate clonal, self-renewing spheres which can generate all the retinal cell types. Since no regenerative properties are seen in situ in the adult mammalian eye, we sought to determine the factors that are involved in the repression of endogenous RSCs. We discovered that factors secreted by the adult lens and cornea block the proliferation of adult RSCs in vitro. Bone morphogenetic protein (BMP)2, BMP4, and secreted frizzled related protein 2 were identified as principal effectors of the anti-proliferative effects on RSCs. As a similar induced quiescence was observed in vitro on both mouse and human RSCs, targeting these molecules in vivo may reactivate RSCs directly in situ in the eyes of the blind.

show abstract

E-Cadherin Regulates Neural Stem Cell Self-Renewal

Cited by 95 publications

References 49 publications

Mechanical control of tissue and organ development

Mechanical control of tissue and organ development

cAMP Promotes Cell Migration Through Cell Junctional Complex Dynamics and Actin Cytoskeleton Remodeling: Implications in Skin Wound Healing

Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells

Contact Info

Product

Resources

About