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planar cell polarity

Eliot Dow, Adrian Jacobo, Sajjad Hossain, Kimberly Siletti, A J Hudspeth
The lateral-line neuromast of the zebrafish displays a restricted, consistent pattern of innervation that facilitates the comparison of microcircuits across individuals, developmental stages, and genotypes. We used serial blockface scanning electron microscopy to determine from multiple specimens the neuromast connectome, a comprehensive set of connections between hair cells and afferent and efferent nerve fibers. This analysis delineated a complex but consistent wiring pattern with three striking characteristics: each nerve terminal is highly specific in receiving innervation from hair cells of a single directional sensitivity; the innervation is redundant; and the terminals manifest a hierarchy of dominance...
June 12, 2018: ELife
Masaki Shigeta, Hirotaka Kanazawa, Takahiko Yokoyama
Inversion of embryonic turning (inv) cystic mice develop multiple renal cysts and are a model for type II nephronophthisis (NPHP2). The defect of planar cell polarity (PCP) by oriented cell division was proposed as the underlying cellular phenotype, while abnormal cell proliferation and apoptosis occur in some polycystic kidney disease models. However, how these cystogenic phenotypes are linked and what is most critical for cystogenesis remain largely unknown. In particular, in early cortical cytogenesis in the inv mutant cystic model, it remains uncertain whether the increased proliferation index results from changes in cell cycle length or cell fate determination...
2018: PloS One
Koji Kikuchi, Akira Nakamura, Masaki Arata, Dongbo Shi, Mami Nakagawa, Tsubasa Tanaka, Tadashi Uemura, Toshihiko Fujimori, Akira Kikuchi, Akiyoshi Uezu, Yasuhisa Sakamoto, Hiroyuki Nakanishi
The Wnt signaling pathway can be grouped into two classes, the β-catenin-dependent and β-catenin-independent pathways. Wnt5a signaling through a β-catenin-independent pathway promotes microtubule (MT) remodeling during cell-substrate adhesion, cell migration, and planar cell polarity formation. Although Wnt5a signaling and MT remodeling are known to form an interdependent regulatory loop, the underlying mechanism remains unknown. Here we show that in HeLa cells, the paralogous MT-associated proteins Map7 and Map7D1 (Map7/7D1) form an interdependent regulatory loop with Disheveled, the critical signal transducer in Wnt signaling...
June 7, 2018: EMBO Reports
Anne Margarete Merks, Marie Swinarski, Alexander Matthias Meyer, Nicola Victoria Müller, Ismail Özcan, Stefan Donat, Alexa Burger, Stephen Gilbert, Christian Mosimann, Salim Abdelilah-Seyfried, Daniela Panáková
Development of a multiple-chambered heart from the linear heart tube is inherently linked to cardiac looping. Although many molecular factors regulating the process of cardiac chamber ballooning have been identified, the cellular mechanisms underlying the chamber formation remain unclear. Here, we demonstrate that cardiac chambers remodel by cell neighbour exchange of cardiomyocytes guided by the planar cell polarity (PCP) pathway triggered by two non-canonical Wnt ligands, Wnt5b and Wnt11. We find that PCP signalling coordinates the localisation of actomyosin activity, and thus the efficiency of cell neighbour exchange...
June 4, 2018: Nature Communications
James P Roy, Michael M Halford, Steven A Stacker
The receptor tyrosine kinases (RTKs) are a well-characterized family of growth factor receptors that have central roles in human disease and are frequently therapeutically targeted. The RYK, ROR, PTK7 and MuSK subfamilies make up an understudied subset of WNT-binding RTKs. Numerous developmental, stem cell and pathological roles of WNTs, in particular WNT5A, involve signalling via these WNT receptors. The WNT-binding RTKs have highly context-dependent signalling outputs and stimulate the β-catenin-dependent, planar cell polarity and/or WNT/Ca2+ pathways...
May 28, 2018: Growth Factors
Chu Chen, Guo-Feng Bao, Guanhua Xu, Yuyu Sun, Zhi-Ming Cui
Facet joint osteoarthritis is common lumbar osteoarthritis characterized by facet joint cartilage degeneration. However, the molecular basis of facet joint osteoarthritis remains largely undetermined. In the current study, we collected facet joint tissue samples from 10 control patients and 48 patients with facet joint osteoarthritis (20 patients with moderate degeneration and 28 with severe degeneration). The control patients underwent internal fixation of the lumbar spine due to vertebral fracture. RNA deep sequencing was performed, and Bioinformatic tools were applied...
2018: Tohoku Journal of Experimental Medicine
Sarita Rani Patnaik, Xun Zhang, Lincoln Biswas, Saeed Akhtar, Xinzhi Zhou, Deva Krupakar Kusuluri, James Reilly, Helen May-Simera, Susan Chalmers, John G McCarron, Xinhua Shu
Ciliopathies are a group of genetically heterogeneous disorders, characterized by defects in cilia genesis or maintenance. Mutations in the RPGR gene and its interacting partners, RPGRIP1 and RPGRIP1L , cause ciliopathies, but the function of their proteins remains unclear. Here we show that knockdown (KD) of RPGR, RPGRIP1 or RPGRIP1L in hTERT-RPE1 cells results in abnormal actin cytoskeleton organization. The actin cytoskeleton rearrangement is regulated by the small GTPase RhoA via the planar cell polarity (PCP) pathway...
May 1, 2018: Oncotarget
Tzong-Hsien Lee, Daniel J Hirst, Ketav Kulkarni, Mark P Del Borgo, Marie-Isabel Aguilar
The molecular analysis of biomolecular-membrane interactions is central to understanding most cellular systems but has emerged as a complex technical challenge given the complexities of membrane structure and composition across all living cells. We present a review of the application of surface plasmon resonance and dual polarization interferometry-based biosensors to the study of biomembrane-based systems using both planar mono- or bilayers or liposomes. We first describe the optical principals and instrumentation of surface plasmon resonance, including both linear and extraordinary transmission modes and dual polarization interferometry...
May 25, 2018: Chemical Reviews
Satish R Ghimire, Evan M Ratzan, Michael R Deans
The cochlea is innervated by neurons that relay sound information from hair cells to central auditory targets. A subset of these are the type II spiral ganglion neurons, which have nociceptive features and contribute to feedback circuits providing neuroprotection in extreme noise. Type II neurons make a distinctive 90° turn towards the cochlear base to synapse with 10-15 outer hair cells. We demonstrate that this axon turning event requires planar cell polarity (PCP) signaling and is disrupted in Vangl2 and Celsr1 knockout mice, and that VANGL2 acts non-autonomously from the cochlea to direct turning...
June 14, 2018: Development
Avais M Daulat, Tania M Puvirajesinghe, Luc Camoin, Jean-Paul Borg
Cell polarity is a vital biological process involved in the building, maintenance and normal functioning of tissues in invertebrates and vertebrates. Unsurprisingly, molecular defects affecting polarity organization and functions have a strong impact on tissue homeostasis, embryonic development and adult life, and may directly or indirectly lead to diseases. Genetic studies have demonstrated the causative effect of several polarity genes in diseases, however much remains to be clarified before a comprehensive view of the molecular organization and regulation of the protein networks associated with polarity proteins is obtained...
May 18, 2018: Journal of Molecular Biology
Suman Gurung, Emilia Asante, Devynn Hummel, Ashley Williams, Oren Feldman-Schultz, Mary C Halloran, Vinoth Sittaramane, Anand Chandrasekhar
Contactin2 (Cntn2)/Transient Axonal Glycoprotein 1 (Tag1), a neural cell adhesion molecule, has established roles in neuronal migration and axon fasciculation in chick and mouse. In zebrafish, antisense morpholino-based studies have indicated roles for cntn2 in the migration of facial branchiomotor (FBM) neurons, the guidance of the axons of the nucleus of the medial longitudinal fascicle (nucMLF), and the outgrowth of Rohon-Beard (RB) central axons. To study functions of Cntn2 in later stages of neuronal development, we generated cntn2 mutant zebrafish using CRISPR-Cas9...
May 16, 2018: Mechanisms of Development
Shinya Ohata, Hideko Uga, Hitoshi Okamoto, Toshiaki Katada
Ras related (R-Ras), a small GTPase, is involved in the maintenance of apico-basal polarity in neuroepithelial cells of the zebrafish hindbrain, axonal collapse in cultured murine hippocampal neurons, and maturation of blood vessels in adult mice. However, the role of R-Ras in neural tube formation remains unknown. Using antisense morpholino oligonucleotides (AMOs), we found that in the spinal cord of zebrafish embryos, the lumen was formed bilaterally in rras morphants, whereas it was formed at the midline in control embryos...
May 14, 2018: Biochemical and Biophysical Research Communications
Thomas Juan, Charles Géminard, Jean-Baptiste Coutelis, Delphine Cerezo, Sophie Polès, Stéphane Noselli, Maximilian Fürthauer
The establishment of left-right (LR) asymmetry is fundamental to animal development, but the identification of a unifying mechanism establishing laterality across different phyla has remained elusive. A cilia-driven, directional fluid flow is important for symmetry breaking in numerous vertebrates, including zebrafish. Alternatively, LR asymmetry can be established independently of cilia, notably through the intrinsic chirality of the acto-myosin cytoskeleton. Here, we show that Myosin1D (Myo1D), a previously identified regulator of Drosophila LR asymmetry, is essential for the formation and function of the zebrafish LR organizer (LRO), Kupffer's vesicle (KV)...
May 16, 2018: Nature Communications
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Chih-Wen Chu is the first author on 'The Ajuba family protein Wtip regulates actomyosin contractility during vertebrate neural tube closure', published in Journal of Cell Science. Chih-Wen is an associate scientist in the lab of Sergei Sokol at Icahn School of Medicine at Mount Sinai, New York, USA, investigating apical constriction and planar cell polarity, with a focus on protein dynamics at the cell junctions...
May 16, 2018: Journal of Cell Science
Giovanna M Collu, Andreas Jenny, Konstantin Gaengel, Ivana Mirkovic, Mei-Ling Chin, Ursula Weber, Michael J Smith, Marek Mlodzik
Planar cell polarity (PCP) instructs tissue patterning in a wide range of organisms from fruit flies to humans. PCP signaling coordinates cell behavior across tissues and is integrated by cells to couple cell fate identity with position in a developing tissue. In the fly eye, PCP signaling is required for the specification of R3 and R4 photoreceptors based upon their positioning relative to the dorso-ventral axis. The 'core' PCP pathway involves the asymmetric localization of two distinct membrane-bound complexes, one containing Frizzled (Fz, required in R3) and the other Van Gogh (Vang, required in R4)...
May 14, 2018: PLoS Genetics
Yi Xie, Hui Miao, J Todd Blankenship
Our understanding of how membrane trafficking pathways function to direct morphogenetic movements and the planar polarization of developing tissues is a new and emerging field. While a central focus of developmental biology has been on how protein asymmetries and cytoskeletal force generation direct cell shaping, the role of membrane trafficking in these processes has been less clear. Here, we review recent advances in Drosophila and vertebrate systems in our understanding of how trafficking events are coordinated with planar cytoskeletal function to drive lasting changes in cell and tissue topologies...
May 14, 2018: Traffic
Jiakun Chen, Gina D Castelvecchi, Nanbing Li-Villarreal, Brian Raught, Andrzej M Krezel, Helen McNeill, Lilianna Solnica-Krezel
Atypical cadherin Dachsous (Dchs) is a conserved regulator of planar cell polarity, morphogenesis, and tissue growth during animal development. Dchs functions in part by regulating microtubules by unknown molecular mechanisms. Here we show that maternal zygotic (MZ) dchs1b zebrafish mutants exhibit cleavage furrow progression defects and impaired midzone microtubule assembly associated with decreased microtubule turnover. Mechanistically, Dchs1b interacts via a conserved motif in its intracellular domain with the tetratricopeptide motifs of Ttc28 and regulates its subcellular distribution...
May 7, 2018: Developmental Cell
Jose M Urbano, Huw W Naylor, Elena Scarpa, Leila Muresan, Bénédicte Sanson
Epithelial folding shapes embryos and tissues during development. Here, we investigate the coupling between epithelial folding and actomyosin-enriched compartmental boundaries. The mechanistic relationship between the two is unclear, because actomyosin-enriched boundaries are not necessarily associated with folds. Also, some cases of epithelial folding occur independently of actomyosin contractility. We investigated the shallow folds called parasegment grooves that form at boundaries between anterior and posterior compartments in the early Drosophila embryo...
April 24, 2018: Development
Tianji Ma, Baiying Li, Ryan Wang, Pik Ki Lau, Yan Huang, Liwen Jiang, Randy Schekman, Yusong Guo
In planar cell polarity (PCP), the epithelial cells are polarized along the plane of the cell surface perpendicular to the classical apical-basal axis, a process mediated by several conserved signaling receptors. Two PCP-signaling proteins, VANGL planar cell polarity protein 2 (Vangl2) and Frizzled6 (Fzd6), are located asymmetrically on opposite boundaries of the cell. Examining sorting of these two proteins at the trans -Golgi network (TGN), we demonstrated previously that the GTP-binding protein ADP-ribosylation factor-related protein 1 (Arfrp1) and the clathrin-associated adaptor protein complex 1 (AP-1) are required for Vangl2 transport from the TGN...
June 1, 2018: Journal of Biological Chemistry
Maureen Cetera, Liliya Leybova, Bradley Joyce, Danelle Devenport
Organ morphogenesis is a complex process coordinated by cell specification, epithelial-mesenchymal interactions and tissue polarity. A striking example is the pattern of regularly spaced, globally aligned mammalian hair follicles, which emerges through epidermal-dermal signaling and planar polarized morphogenesis. Here, using live-imaging, we discover that developing hair follicles polarize through dramatic cell rearrangements organized in a counter-rotational pattern of cell flows. Upon hair placode induction, Shh signaling specifies a radial pattern of progenitor fates that, together with planar cell polarity, induce counter-rotational rearrangements through myosin and ROCK-dependent polarized neighbour exchanges...
May 2018: Nature Cell Biology
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