scholarly journals Glypican 4 regulates planar cell polarity of endoderm cells by controlling the localization of Cadherin 2

Development ◽  
2021 ◽  
Author(s):  
Anurag Kakkerla Balaraju ◽  
Bo Hu ◽  
Juan J Rodriguez ◽  
Matthew Murry ◽  
Fang Lin
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Molecular Mechanisms ◽  
Sulfate Proteoglycan ◽  
Endodermal Cell ◽  
Convergence And Extension ◽  
Pcp Signaling ◽  
Endodermal Cells ◽  
Canonical Wnt

Non-canonical Wnt/Planar Cell Polarity (Wnt/PCP) signaling has been implicated in endoderm morphogenesis. However, the underlying cellular and molecular mechanisms of this process are unclear. We found that during convergence and extension (C&E) in zebrafish, gut endodermal cells are polarized mediolaterally, with GFP-Vangl2 enriched at the anterior edges. Endoderm cell polarity is lost, and intercalation is impaired, in the absence of glypican 4 (gpc4), a heparan-sulfate proteoglycan that promotes Wnt/PCP signaling, suggesting that this signaling is required for endodermal cell polarity. Live imaging revealed that endoderm C&E is accomplished by polarized cell protrusions and junction remodeling, which are impaired in gpc4-deficient endodermal cells. Furthermore, in the absence of gpc4, Cadherin 2 expression on the endodermal cell surface is increased due to impaired Rab5c-mediated endocytosis, which partially accounts for the endodermal defects in these mutants.These findings indicate that Gpc4 regulates endodermal planar cell polarity during endoderm C&E by influencing localization of Cadherin 2. Thus, our study uncovers a new mechanism by which Gpc4 regulates planar cell polarity and reveals the role of Wnt/PCP signaling in endoderm morphogenesis.

scholarly journals Update on the Role of the Non-Canonical Wnt/Planar Cell Polarity Pathway in Neural Tube Defects

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1198 ◽  
Author(s):  
Wang ◽  
Marco ◽  
Capra ◽  
Kibar
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Neural Tube Closure ◽  
Convergent Extension ◽  
Complex Genetics ◽  
Pcp Signaling ◽  
Canonical Wnt

Neural tube defects (NTDs), including spina bifida and anencephaly, represent the most severe and common malformations of the central nervous system affecting 0.7–3 per 1000 live births. They result from the failure of neural tube closure during the first few weeks of pregnancy. They have a complex etiology that implicate a large number of genetic and environmental factors that remain largely undetermined. Extensive studies in vertebrate models have strongly implicated the non-canonical Wnt/planar cell polarity (PCP) signaling pathway in the pathogenesis of NTDs. The defects in this pathway lead to a defective convergent extension that is a major morphogenetic process essential for neural tube elongation and subsequent closure. A large number of genetic studies in human NTDs have demonstrated an important role of PCP signaling in their etiology. However, the relative contribution of this pathway to this complex etiology awaits a better picture of the complete genetic architecture of these defects. The emergence of new genome technologies and bioinformatics pipelines, complemented with the powerful tool of animal models for variant interpretation as well as significant collaborative efforts, will help to dissect the complex genetics of NTDs. The ultimate goal is to develop better preventive and counseling strategies for families affected by these devastating conditions.

scholarly journals STAT3 noncell-autonomously controls planar cell polarity during zebrafish convergence and extension

2004 ◽  
Vol 166 (7) ◽  
pp. 975-981 ◽  
Author(s):  
Chiemi Miyagi ◽  
Susumu Yamashita ◽  
Yusuke Ohba ◽  
Hisayoshi Yoshizaki ◽  
Michiyuki Matsuda ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Cell Polarization ◽  
Rhoa Activity ◽  
Stat3 Signaling ◽  
Convergence And Extension ◽  
Pcp Signaling ◽  
Autonomous Activity ◽  
Rhoa Signaling ◽  
Transcription 3

Zebrafish signal transducer and activator of transcription 3 (STAT3) controls the cell movements during gastrulation. Here, we show that noncell-autonomous activity of STAT3 signaling in gastrula organizer cells controls the polarity of neighboring cells through Dishevelled-RhoA signaling in the Wnt-planar cell polarity (Wnt-PCP) pathway. In STAT3-depleted embryos, although all the known molecules in the Wnt-PCP pathway were expressed normally, the RhoA activity in lateral mesendodermal cells was down-regulated, resulting in severe cell polarization defects in convergence and extension movements identical to Strabismus-depleted embryos. Cell-autonomous activation of Wnt-PCP signaling by ΔN-dishevelled rescued the defect in cell elongation, but not the orientation of lateral mesendodermal cells in STAT3-depleted embryos. The defect in the orientation could be rescued by transplantation of shield cells having noncell-autonomous activity of STAT3 signaling. These results suggest that the cells undergoing convergence and extension movement may sense the gradient of signaling molecules, which are expressed in gastrula organizer by STAT3 and noncell-autonomously activate PCP signaling in neighboring cells during zebrafish gastrulation.

The role of the non-canonical Wnt–planar cell polarity pathway in neural crest migration

2013 ◽  
Vol 457 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Roberto Mayor ◽  
Eric Theveneau
Keyword(s):  
Neural Crest ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Neural Crest Cells ◽  
Contact Inhibition ◽  
Stem Cell Population ◽  
Planar Cell Polarity Pathway ◽  
Canonical Wnt ◽  
Neural Crest Migration

The neural crest is an embryonic stem cell population whose migratory behaviour has been likened to malignant invasion. The neural crest, as does cancer, undergoes an epithelial-to-mesenchymal transition and migrates to colonize almost all the tissues of the embryo. Neural crest cells exhibit collective cell migration, moving in streams of high directionality. The migratory neural crest streams are kept in shape by the presence of negative signals in their vicinity. The directionality of the migrating neural crest is achieved by contact-dependent cell polarization, in a phenomenon called contact inhibition of locomotion. Two cells experiencing contact inhibition of locomotion move away from each other after collision. However, if the cell density is high only cells exposed to a free edge can migrate away from the cluster leading to the directional migration of the whole group. Recent work performed in chicks, zebrafish and frogs has shown that the non-canonical Wnt–PCP (planar cell polarity) pathway plays a major role in neural crest migration. PCP signalling controls contact inhibition of locomotion between neural crest cells by localizing different PCP proteins at the site of cell contact during collision and locally regulating the activity of Rho GTPases. Upon collision RhoA (ras homologue family member A) is activated, whereas Rac1 is inhibited at the contact between two migrating neural crest cells, leading to the collapse of protrusions and the migration of cells away from one another. The present review summarizes the mechanisms that control neural crest migration and focuses on the role of non-canonical Wnt or PCP signalling in this process.

scholarly journals Nodal and planar cell polarity signaling cooperate to regulate zebrafish convergence and extension gastrulation movements

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Margot LK Williams ◽  
Lilianna Solnica-Krezel
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Embryonic Axis ◽  
Dependent Manner ◽  
Nodal Signaling ◽  
Cell Behaviors ◽  
Signaling Systems ◽  
Convergence And Extension ◽  
Pcp Signaling ◽  
Axis Extension

During vertebrate gastrulation, convergence and extension (C and E) of the primary anteroposterior (AP) embryonic axis is driven by polarized mediolateral (ML) cell intercalations and is influenced by AP axial patterning. Nodal signaling is essential for patterning of the AP axis while planar cell polarity (PCP) signaling polarizes cells with respect to this axis, but how these two signaling systems interact during C and E is unclear. We find that the neuroectoderm of Nodal-deficient zebrafish gastrulae exhibits reduced C and E cell behaviors, which require Nodal signaling in both cell- and non-autonomous fashions. PCP signaling is partially active in Nodal-deficient embryos and its inhibition exacerbates their C and E defects. Within otherwise naïve zebrafish blastoderm explants, however, Nodal induces C and E in a largely PCP-dependent manner, arguing that Nodal acts both upstream of and in parallel with PCP during gastrulation to regulate embryonic axis extension cooperatively.

scholarly journals Coupling Planar Cell Polarity Signaling to Morphogenesis

2002 ◽  
Vol 2 ◽  
pp. 434-454 ◽  
Author(s):  
Jeffrey D. Axelrod ◽  
Helen McNeill
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Fruit Fly ◽  
Convergent Extension ◽  
Cytoskeletal Reorganization ◽  
Directional Information ◽  
Cochlear Hair Cell ◽  
Cellular Asymmetry ◽  
Pcp Signaling ◽  
Unknown Signal

Epithelial cells and other groups of cells acquire a polarity orthogonal to their apical–basal axes, referred to as Planar Cell Polarity (PCP). The process by which these cells become polarized requires a signaling pathway using Frizzled as a receptor. Responding cells sense cues from their environment that provide directional information, and they translate this information into cellular asymmetry. Most of what is known about PCP derives from studies in the fruit fly,Drosophila. We review what is known about how cells translate an unknown signal into asymmetric cytoskeletal reorganization. We then discuss how the vertebrate processes of convergent extension and cochlear hair-cell development may relate toDrosophilaPCP signaling.

scholarly journals Celsr1 and CAMSAP3 differently regulate intercellular and intracellular cilia orientation in oviduct multiciliated cells

2020 ◽  
Author(s):  
Fumiko Matsukawa Usami ◽  
Masaki Arata ◽  
Dongbo Shi ◽  
Sanae Oka ◽  
Yoko Higuchi ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Molecular Mechanisms ◽  
The Other ◽  
Basal Bodies ◽  
Generating Functional ◽  
Tissue Polarity ◽  
Other Hand ◽  
Multiciliated Cells ◽  
Polarity Regulation

SummaryThe molecular mechanisms by which cilia orientation is coordinated within and between multiciliated cells (MCCs) is not fully understood. By observing the orientation of basal bodies (BB) in MCCs of mouse oviducts, here, we show that Celsr1, a planar cell polarity (PCP) factor involved in tissue polarity regulation, is dispensable for determining BB orientation in individual cells, whereas CAMSAP3, a microtubule minus-end regulator, is critical for this process but not for PCP. MCCs exhibit a characteristic BB orientation and microtubule gradient along the tissue axis, and these intracellular polarities were maintained in the cells lacking Celsr1, although the intercellular coordination of the polarities was partly disrupted. On the other hand, CAMSAP3 regulated the assembly of microtubules interconnecting BBs by localizing at the BBs, and its mutation led to disruption of intracellular coordination of BB orientation, but not affecting PCP factor localization. Thus, both Celsr1 and CAMSAP3 are responsible for BB orientation but in distinct ways; and therefore, their cooperation should be critical for generating functional multiciliated tissues.

scholarly journals Non-Canonical Wnt Signaling Regulates Cochlear Outgrowth and Planar Cell Polarity via Gsk3β Inhibition

2021 ◽  
Vol 9 ◽  
Author(s):  
Andre Landin Malt ◽  
Shaylyn Clancy ◽  
Diane Hwang ◽  
Alice Liu ◽  
Connor Smith ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Small Gtpase ◽  
Hair Bundle ◽  
Apical Surface ◽  
Canonical Wnt Signaling ◽  
Genetic Rescue ◽  
Genetic Ablation ◽  
Canonical Wnt

During development, sensory hair cells (HCs) in the cochlea assemble a stereociliary hair bundle on their apical surface with planar polarized structure and orientation. We have recently identified a non-canonical, Wnt/G-protein/PI3K signaling pathway that promotes cochlear outgrowth and coordinates planar polarization of the HC apical cytoskeleton and alignment of HC orientation across the cochlear epithelium. Here, we determined the involvement of the kinase Gsk3β and the small GTPase Rac1 in non-canonical Wnt signaling and its regulation of the planar cell polarity (PCP) pathway in the cochlea. We provided the first in vivo evidence for Wnt regulation of Gsk3β activity via inhibitory Ser9 phosphorylation. Furthermore, we carried out genetic rescue experiments of cochlear defects caused by blocking Wnt secretion. We showed that cochlear outgrowth was partially rescued by genetic ablation of Gsk3β but not by expression of stabilized β-catenin; while PCP defects, including hair bundle polarity and junctional localization of the core PCP proteins Fzd6 and Dvl2, were partially rescued by either Gsk3β ablation or constitutive activation of Rac1. Our results identify Gsk3β and likely Rac1 as downstream components of non-canonical Wnt signaling and mediators of cochlear outgrowth, HC planar polarity, and localization of a subset of core PCP proteins in the cochlea.

scholarly journals SHROOM3 is a novel component of the planar cell polarity pathway whose disruption causes congenital heart disease

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Alison Schmidt ◽  
Matthew Durbin, MS MD ◽  
James O’Kane, MS ◽  
Stephanie M. Ware, MD PHD
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Signaling Pathway ◽  
Cell Polarity ◽  
Congenital Heart ◽  
Planar Cell Polarity ◽  
Cardiac Development ◽  
Genetic Interaction ◽  
Compound Heterozygous ◽  
Pcp Signaling

Congenital heart disease (CHD) is the most common cause of death due to birth defects. Despite CHD frequency, the etiology remains mostly unknown. Understanding CHD genetics and elucidating disease mechanism will help establish prognosis, identify comorbidity risks, and develop targeted therapies. CHD often results from disrupted cytoarchitecture and signaling pathways. We have identified a novel CHD candidate SHROOM3, a protein associated with the actin cytoskeleton and the Wnt/Planar Cell Polarity (PCP) signaling pathway. SHROOM3 induces actomyosin constriction within the apical side of cells and is implicated in neural tube defects and chronic renal failure in humans. A recent study demonstrated that SHROOM3 interacts with Dishevelled2 (DVL2), a component of the PCP signaling pathway, suggesting that SHROOM3 serves as an important link between acto-myosin constriction and PCP signaling. PCP signaling establishes cell polarity required for multiple developmental processes, and is required for cardiac development. In Preliminary data we utilized a Shroom3 gene-trap mouse (Shroom3gt/gt) to demonstrated that SHROOM3 disruption leads to cardiac defects phenocopy PCP disruption. We also demonstrate that patients with CHD phenotypes have rare and potentially damaging SHROOM3 variants within SHROOM3’s PCP-binding domain. We hypothesize SHROOM3 is a novel terminal effector of PCP signaling, and disruption is a novel contributor to CHD. To test this, we assessed genetic interaction between SHROOM3 and PCP during cardiac development and the ultimate effect on cell structure and movement. Heterozygous Shroom3+/gt mice and heterozygous Dvl2 +/- mice are phenotypically normal. We demonstrated genetic interaction between SHROOM3 and PCP signaling by generating compound heterozygous Shroom3+/gt ;Dvl2 +/- mice and identifying a Double Outlet Right Ventricle and Ventricular Septal Defect in one embryo. We also observed fewer compound heterozygous mice than anticipated by Mendelian rations (observed: 18.4%; expected: 25%; n=76), suggesting potential lethality in utero. Immunohistochemistry demonstrates disrupted actomyosin in the SHROOM3gt/gt mice, characteristic of PCP disruption. These data help strengthen SHROOM3 as a novel CHD candidate gene and a component of the PCP Signaling pathway. Further characterization of this gene is important for CHD diagnosis and therapeutic development.

scholarly journals Planar Cell Polarity Signaling Pathway in Congenital Heart Diseases

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Gang Wu ◽  
Jiao Ge ◽  
Xupei Huang ◽  
Yimin Hua ◽  
Dezhi Mu
Keyword(s):  
Signaling Pathway ◽  
Cell Polarity ◽  
Congenital Heart ◽  
Planar Cell Polarity ◽  
Heart Diseases ◽  
Multiple Roles ◽  
Cardiac Differentiation ◽  
Tissue Polarity ◽  
Cardiac Disorder ◽  
Pcp Signaling

Congenital heart disease (CHD) is a common cardiac disorder in humans. Despite many advances in the understanding of CHD and the identification of many associated genes, the fundamental etiology for the majority of cases remains unclear. The planar cell polarity (PCP) signaling pathway, responsible for tissue polarity inDrosophilaand gastrulation movements and cardiogenesis in vertebrates, has been shown to play multiple roles during cardiac differentiation and development. The disrupted function of PCP signaling is connected to some CHDs. Here, we summarize our current understanding of how PCP factors affect the pathogenesis of CHD.

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