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 The chromatin factor Gon4l regulates embryonic axis extension by promoting mediolateral cell polarity and notochord boundary formation through negative regulation of cell adhesion

2017 ◽  
Author(s):  
Margot L K Williams ◽  
Atsushi Sawada ◽  
Terin Budine ◽  
Chunyue Yin ◽  
Paul Gontarz ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Embryonic Axis ◽  
Negative Regulator ◽  
Embryonic Patterning ◽  
Boundary Formation ◽  
Ugly Duckling ◽  
Genetic Mechanisms ◽  
Pcp Signaling ◽  
Axis Extension

Anteroposterior axis extension during vertebrate gastrulation requires cell proliferation, embryonic patterning, and morphogenesis to be spatiotemporally coordinated, but the underlying genetic mechanisms remain poorly understood. Here we define a role for the conserved chromatin factor Gon4l, encoded by ugly duckling (udu), in coordinating tissue patterning and axis extension during zebrafish gastrulation. Although identified as a recessive enhancer of short axis phenotypes in planar cell polarity (PCP) mutants, we found that Gon4l functions in a genetically independent, partially overlapping fashion with PCP signaling to regulate mediolateral cell polarity underlying axis extension in part by promoting notochord boundary formation. We identified direct genomic targets of Gon4l and found that it acts as both a positive and negative regulator of gene expression, including limiting expression of the cell-cell and cell-matrix adhesion molecules EpCAM and Integrinα3b. Excess epcam or itga3b in wild-type gastrulae phenocopied notochord boundary defects of udu mutants, while downregulation of itga3b suppressed them. By promoting formation of this anteroposteriorly aligned boundary and associated cell polarity, Gon4l cooperates with PCP signaling to coordinate morphogenesis with the anteroposterior embryonic axis.

scholarly journals A mesoderm-independent role for Nodal signaling in convergence & extension gastrulation movements

2019 ◽  
Author(s):  
Margot L.K. Williams ◽  
Lilianna Solnica-Krezel
Keyword(s):  
Cell Fate ◽  
Planar Cell Polarity ◽  
Cell Polarization ◽  
Nodal Signaling ◽  
Embryonic Patterning ◽  
Embryonic Axes ◽  
Pcp Signaling ◽  
A Cell ◽  
Cellular Machinery ◽  
Axis Extension

ABSTRACTDuring embryogenesis, the distinct morphogenetic cell behavior programs that shape tissues are influenced both by the fate of cells and their position with respect to the embryonic axes, making embryonic patterning a prerequisite for morphogenesis. These two essential processes must therefore be coordinated in space and time to ensure proper development, but mechanisms by which patterning information is translated to the cellular machinery that drives morphogenesis remain poorly understood. Here, we address the role of Nodal morphogen signaling at the intersection of cell fate specification, patterning, and anteroposterior (AP) axis extension in zebrafish gastrulae and embryonic explants. AP axis extension is impaired in Nodal-deficient embryos, but it is unclear whether this defect is strictly secondary to their severe mesendoderm deficiencies or also results from loss of Nodal signaling per se. We find that convergence & extension (C&E) gastrulation movements and underlying mediolateral (ML) cell polarization are reduced in the neuroectoderm of Nodal-deficient mutants and exacerbated by simultaneous disruption of Planar Cell Polarity (PCP) signaling, demonstrating at least partially parallel functions of Nodal and PCP. ML polarity of mutant neuroectoderm cells is not fully restored upon transplantation into wild-type gastrulae, demonstrating a cell autonomous, mesoderm-independent role for Nodal in neural cell polarization. This is further demonstrated by the ability of Nodal ligands to promote neuroectoderm-driven C&E of naïve blastoderm explants in a tissue-autonomous fashion. Finally, temporal manipulation of signaling reveals that Nodal contributes to neural C&E in explants after mesoderm is specified and promotes C&E even in the absence of mesoderm. Together these results reveal a mesoderm-independent, cell-autonomous role for Nodal signaling in neural C&E that may cooperate with previously-described mesoderm-dependent mechanisms to drive AP embryonic axis extension.

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.

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 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 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.

scholarly journals Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis

Science ◽  
2010 ◽  
Vol 329 (5997) ◽  
pp. 1337-1340 ◽  
Author(s):  
Su Kyoung Kim ◽  
Asako Shindo ◽  
Tae Joo Park ◽  
Edwin C. Oh ◽  
Srimoyee Ghosh ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Control Point ◽  
Cell Movement ◽  
Cytoskeletal Proteins ◽  
Pcp Signaling ◽  
Cellular Machinery ◽  
And Migration ◽  
Controlling Behaviors ◽  
Shed Light

The planar cell polarity (PCP) signaling pathway governs collective cell movements during vertebrate embryogenesis, and certain PCP proteins are also implicated in the assembly of cilia. The septins are cytoskeletal proteins controlling behaviors such as cell division and migration. Here, we identified control of septin localization by the PCP protein Fritz as a crucial control point for both collective cell movement and ciliogenesis in Xenopus embryos. We also linked mutations in human Fritz to Bardet-Biedl and Meckel-Gruber syndromes, a notable link given that other genes mutated in these syndromes also influence collective cell movement and ciliogenesis. These findings shed light on the mechanisms by which fundamental cellular machinery, such as the cytoskeleton, is regulated during embryonic development and human disease.

scholarly journals BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways

2011 ◽  
Vol 192 (1) ◽  
pp. 171-188 ◽  
Author(s):  
Vinicio A. de Jesus Perez ◽  
Ziad Ali ◽  
Tero-Pekka Alastalo ◽  
Fumiaki Ikeno ◽  
Hirofumi Sawada ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Planar Cell Polarity ◽  
Bone Morphogenetic Protein 2 ◽  
Dependent Manner ◽  
Morphogenetic Protein ◽  
Injury Model ◽  
Pcp Signaling ◽  
Integrin Linked Kinase ◽  
Wnt Pathways

We present a novel cell-signaling paradigm in which bone morphogenetic protein 2 (BMP-2) consecutively and interdependently activates the wingless (Wnt)–β-catenin (βC) and Wnt–planar cell polarity (PCP) signaling pathways to facilitate vascular smooth muscle motility while simultaneously suppressing growth. We show that BMP-2, in a phospho-Akt–dependent manner, induces βC transcriptional activity to produce fibronectin, which then activates integrin-linked kinase 1 (ILK-1) via α4-integrins. ILK-1 then induces the Wnt–PCP pathway by binding a proline-rich motif in disheveled (Dvl) and consequently activating RhoA-Rac1–mediated motility. Transfection of a Dvl mutant that binds βC without activating RhoA-Rac1 not only prevents BMP-2–mediated vascular smooth muscle cell motility but promotes proliferation in association with persistent βC activity. Interfering with the Dvl-dependent Wnt–PCP activation in a murine stented aortic graft injury model promotes extensive neointima formation, as shown by optical coherence tomography and histopathology. We speculate that, in response to injury, factors that subvert BMP-2–mediated tandem activation of Wnt–βC and Wnt–PCP pathways contribute to obliterative vascular disease in both the systemic and pulmonary circulations.

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