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planar cell polarity

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 adaptor complex 1 (AP-1) are required for Vangl2 transport from the TGN...
April 17, 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...
April 16, 2018: Nature Cell Biology
Paul N Adler
The frizzled pathway regulates the planar polarity of epithelial cells. In insects this is manifested by the polarity of cuticular structures such as hairs (trichomes) and sensory bristles. A variety of evidence has established that this is achieved by regulating the subcellular location for activating the cytoskeleton in the epithelial cells. How this is accomplished is still poorly understood. In the best-studied tissue, the Drosophila pupal wing two important cytoskeletal regulators have been identified...
April 9, 2018: Progress in Biophysics and Molecular Biology
Zhongzhong Chen, Yunping Lei, Xuanye Cao, Yufang Zheng, Fang Wang, Yihua Bao, Rui Peng, Richard H Finnell, Ting Zhang, Hongyan Wang
BACKGROUND: Mouse homozygous mutants in Wnt/planar cell polarity (PCP) pathway genes have been shown to cause neural tube defects (NTDs) through the disruption of normal morphogenetic processes critical to neural tube closure (NTC). Knockout mice that are heterozygotes of single PCP genes likely fail to produce NTD phenotypes, yet damaging variants detected in human NTDs are almost always heterozygous, suggesting that other deleterious interacting variants are likely to be present. Nonetheless, the Wnt/PCP pathway remains a genetic hotspot...
April 4, 2018: BMC Medical Genomics
Margot L K Williams, Atsushi Sawada, Terin Budine, Chunyue Yin, Paul Gontarz, Lilianna Solnica-Krezel
Anteroposterior (AP) axis extension during gastrulation requires 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 through direct positive and negative regulation of gene expression. Although identified as a recessive enhancer of impaired axis extension in planar cell polarity (PCP) mutants, udu 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...
April 3, 2018: Nature Communications
Bo Gao, Rieko Ajima, Wei Yang, Chunyu Li, Hai Song, Matthew J Anderson, Robert R Liu, Mark B Lewandoski, Terry P Yamaguchi, Yingzi Yang
Embryonic morphogenesis of a complex organism requires proper regulation of patterning and directional growth. The Planar Cell Polarity (PCP) signaling is emerging as a critical evolutionarily conserved mechanism whereby directional information is conveyed. PCP is thought to be established by global cues, and recent studies have revealed an instructive role of Wnt signaling gradient in epithelia tissues of both invertebrates and vertebrates. However, it remains unclear whether Wnt/PCP signaling is coordinately regulated with embryonic patterning during morphogenesis...
April 3, 2018: Development
Oriol Viader-Llargués, Valerio Lupperger, Laura Pola-Morell, Carsten Marr, Hernán López-Schier
Despite the intrinsically stochastic nature of damage, sensory organs recapitulate normal architecture during repair to maintain function. Here we present a quantitative approach that combines live cell-lineage tracing and multifactorial classification by machine learning to reveal how cell identity and localization are coordinated during organ regeneration. We use the superficial neuromasts in larval zebrafish, which contain three cell classes organized in radial symmetry and a single planar-polarity axis...
March 29, 2018: ELife
Gabriel L Galea, Oleksandr Nychyk, Matteo A Mole, Dale Moulding, Dawn Savery, Evanthia Nikolopoulou, Deborah J Henderson, Nicholas D E Greene, Andrew J Copp
Human mutations in the planar cell polarity component VANGL2 are associated with the neural tube defect spina bifida. Homozygous Vangl2 mutation in mice prevents initiation of neural tube closure, precluding analysis of its subsequent roles in neurulation. Spinal neurulation involves rostral-to-caudal 'zippering' until completion of closure is imminent, when a caudal-to-rostral closure point, 'Closure 5', arises at the caudal-most extremity of the posterior neuropore (PNP). Here, we used Grhl3Cre to delete Vangl2 in the surface ectoderm (SE) throughout neurulation and in an increasing proportion of PNP neuroepithelial cells at late neurulation stages...
March 21, 2018: Disease Models & Mechanisms
Shixuan Wang, Aimin Liu, Guangyu Wu, Han-Fei Ding, Shuang Huang, Stanley Nahman, Zheng Dong
Intu is known as a ciliogenesis and planar polarity effector (CPLANE) protein. Although roles for Intu have been reported during embryonic development and in the context of developmental disorders, its function and regulation in adult tissues remain poorly understood. Here we show that ablation of Intu specifically in kidney proximal tubules aggravates renal ischemia-reperfusion injury, and leads to defective post-injury ciliogenesis. We identify signal transducer and activator of transcription 1 (STAT1) as a novel interacting partner of Intu...
March 26, 2018: Nature Communications
Bingfang Xu, Sérgio A A Santos, Barry T Hinton
Wolffian duct morphogenesis must be highly coordinated with its specialized function of providing an optimal microenvironment for sperm maturation. Without normal Wolffian duct morphogenesis, male infertility will result. Our previous study showed that mediolateral and radial intercalation of epithelial and mesenchymal cells respectively, were major drivers of ductal elongation and were regulated by protein tyrosine kinase 7 (PTK7), a member of the planar cell polarity (PCP) non-canonical Wnt pathway. To understand the mechanism by which PTK7 regulates cell rearrangement/intercalation, we investigated the integrity of the extracellular matrix (ECM) and the activity of intracellular cytoskeleton mediators following loss of Ptk7...
March 23, 2018: Developmental Biology
Yanqing Geng, Rufei Gao, Xueqing Liu, Xuemei Chen, Shangjing Liu, Yubin Ding, Xinyi Mu, Yingxiong Wang, Junlin He
Folate deficiency results in abnormal embryonic development, but the underlying mechanisms remain to be comprehensively investigated. Mutation of Vangl genes belonging to the planar cell polarity (PCP) pathway is associated with abnormal embryonic development, but the effect of folate deficiency on the PCP pathway is unclear. In this study, we found that folate deficiency inhibited Vangl gene expression and Vangl protein binding to the ligand Dvl. As a methyl donor, folate can chemically alter the DNA methylation levels of genomic sequences...
March 25, 2018: Journal of Cellular Physiology
Linlin Wang, Yanhui Xiao, Tian Tian, Lei Jin, Yunping Lei, Richard H Finnell, Aiguo Ren
Neural tube defects (NTDs) are considered to be a complex genetic disorder, although the identity of the genetic factors remains largely unknown. Mouse model studies suggest a multifactorial oligogenic pattern of inheritance for NTDs, yet evidence from published human studies is surprisingly absent. In the present study, targeted next-generation sequencing was performed to screen for DNA variants in the entire coding regions and intron-exon boundaries of targeted genes using DNA samples from 510 NTD cases. These candidate genes were PCP genes, including VANGL1, VANGL2, CELSR1, SCRIB, DVL2, DVL3 and PTK7...
March 18, 2018: Molecular Genetics and Metabolism
Ding Li, Jianbo Wang
The mammalian heart is the first organ to form and is critical for embryonic survival and development. With an occurrence of 1%, congenital heart defects (CHDs) are also the most common birth defects in humans, and major cause of childhood morbidity and mortality (Hoffman and Kaplan in J Am Coll Cardiol 39(12):1890-1900, 2002; Samanek in Cardiol Young 10(3):179-185, 2000). Understanding how the heart forms will not only help to determine the etiology and to design diagnostic and therapeutic approaches for CHDs, but may also provide insight into regenerative medicine to repair injured adult hearts...
March 22, 2018: Pediatric Cardiology
Ritika S Joshi, Dipanwita Das Mukherjee, Subhendu Chakrabarty, Ansie Martin, Manojkumar Jadhao, Gopal Chakrabarti, Angshuman Sarkar, Sujit Kumar Ghosh
In the development of small molecule drug candidates, naphthalimide based compounds hold a very important position as potent anti-cancer agents with considerable safety in drug discoveries. Being synthetically and readily accessible, naphthalimide compounds with planar architecture have been developed mostly as DNA targeting intercalators. However, in this article, we demonstrate, for the first time, wherein an unfused naphthalimide-benzothiazole bichromophoric compound 2-(6-chlorobenzo[d] thiazol-2-yl)-1H-benzo[de] isoquinoline-1,3(2H)-dione (CBIQD), designed and synthesized by our group, seem to expand the bioactivity of naphthalimide as anti-mitotic agents also...
March 21, 2018: Journal of Physical Chemistry. B
Miki Iwasaki, Junpei Kuroda, Koichi Kawakami, Hironori Wada
Bone is a connective tissue composed of many cell types, including osteoblasts. How bones acquire their unique size and shape during development remains poorly understood. Herein we investigated the molecular and cellular mechanisms of bone morphogenesis in the zebrafish scale by using transgenic lines to enable visualization of specific types of osteoblasts. We demonstrate that the zebrafish scale contains three distinct types of osteoblasts: (i) a monolayer of central osteoblasts along the inner surface of scales; (ii) marginal osteoblasts elongated along the scale edge; and (iii) submarginal osteoblasts located between the central and marginal osteoblast populations...
March 7, 2018: Developmental Biology
Sun K Kim, Siwei Zhang, Michael E Werner, Eva J Brotslaw, Jennifer W Mitchell, Mohamed M Altabbaa, Brian J Mitchell
Most epithelial cells polarize along the axis of the tissue, a feature known as planar cell polarity (PCP). The initiation of PCP requires cell-cell signaling via the noncanonical Wnt/PCP pathway. Additionally, changes in the cytoskeleton both facilitate and reflect this polarity. We have identified CLAMP/Spef1 as a novel regulator of PCP signaling. In addition to decorating microtubules (MTs) and the ciliary rootlet, a pool of CLAMP localizes at the apical cell cortex. Depletion of CLAMP leads to the loss of PCP protein asymmetry, defects in cilia polarity, and defects in the angle of cell division...
March 7, 2018: Journal of Cell Biology
Michelle L Stoller, Orvelin Roman, Michael R Deans
The organization of polarized stereociliary bundles is critical for the function of the inner ear sensory receptor hair cells that detect sound and motion, and these cells present a striking example of Planar Cell Polarity (PCP); the coordinated orientation of polarized structures within the plane of an epithelium. PCP is best understood in Drosophila where the essential genes regulating PCP were first discovered, and functions for the core PCP proteins encoded by these genes have been deciphered through phenotypic analysis of core PCP gene mutants...
March 3, 2018: Developmental Biology
Xiwei Shan, Lyl Tomlinson, Qian Yang, Holly Colognato
The regulatory mechanisms that control neural stem cell (NSC) activation in the adult ventricular-subventricular zone (V-SVZ) stem cell niche have been the focus of intense investigation, yet how the niche first develops and organizes is poorly understood. Here, we examined matrix metalloproteinases (MMPs) for potential roles in V-SVZ stem cell niche development. MMP12 was found to promote appropriate niche cellular arrangements, the formation of specialized niche extracellular matrix, and the translational planar cell polarity of ependymal cells that surround and support niche NSCs...
March 13, 2018: Stem Cell Reports
Madeline N Hayes, Karin McCarthy, Alexander Jin, Mariana L Oliveira, Sowmya Iyer, Sara P Garcia, Sivasish Sindiri, Berkley Gryder, Zainab Motala, G Petur Nielsen, Jean-Paul Borg, Matt van de Rijn, David Malkin, Javed Khan, Myron S Ignatius, David M Langenau
Tumor growth and relapse are driven by tumor propagating cells (TPCs). However, mechanisms regulating TPC fate choices, maintenance, and self-renewal are not fully understood. Here, we show that Van Gogh-like 2 (Vangl2), a core regulator of the non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway, affects TPC self-renewal in rhabdomyosarcoma (RMS)-a pediatric cancer of muscle. VANGL2 is expressed in a majority of human RMS and within early mononuclear progenitor cells. VANGL2 depletion inhibited cell proliferation, reduced TPC numbers, and induced differentiation of human RMS in vitro and in mouse xenografts...
March 1, 2018: Cell Stem Cell
Haiqi Chen, Xiang Xiao, Wing-Yee Lui, Will M Lee, C Yan Cheng
During spermatogenesis, developing elongating/elongated spermatids are highly polarized cells, displaying unique apico-basal polarity. For instance, the heads of spermatids align perpendicular to the basement membrane with their tails pointing to the tubule lumen. Thus, the maximal number of spermatids are packed within the limited space of the seminiferous epithelium to support spermatogenesis.  Herein, we reported findings that  elongating/elongated spermatids displayed planar cell polarity (PCP) in adult rat testes in which the proximal end of polarized spermatid heads were aligned uniformly across the plane of the seminiferous epithelium based on studies  using confocal microscopy and 3-dimensional (D) reconstruction of the seminiferous tubules...
March 1, 2018: Cell Death & Disease
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