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| Open AccessMechanical control of neural plate folding by apical domain alteration
Theoretical and experimental observations argue that apical domain heterogeneity in the neural plate is a tug-of-war contest between constricted and elongated cells. This competition likely reflects mechanical forces operating during tissue bending.
- Miho Matsuda
- , Jan Rozman
- & Sergei Y. Sokol
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Article
| Open AccessContractile ring mechanosensation and its anillin-dependent tuning during early embryogenesis
Contractile ring formation, positioning, and closure is influenced by tissue mechanics, though how this information is transmitted is unclear. Here they show that Anillin is critical for a mechanosensitive pathway that drives cytokinesis and contractile ring closure.
- Christina Rou Hsu
- , Gaganpreet Sangha
- & Kenji Sugioka
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Article
| Open AccessCXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
Regulation of cell polarity is key to ensure directed cell migration. Here, Atkins et al. identify the primary cilium cAMP/cGMP ratio as a master regulator of the cell polarity of migrating cortical interneurons downstream of the CXCL12 chemokine.
- Melody Atkins
- , Maud Wurmser
- & Christine Métin
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Article
| Open AccessA dynamic partitioning mechanism polarizes membrane protein distribution
Different membrane proteins dynamically polarize to organize signal transduction, but the underlying mechanism is unclear. Here, the authors show that a differential diffusion mediated partitioning process is sufficient to drive such spatiotemporal patterning of membrane-associated signaling proteins.
- Tatsat Banerjee
- , Satomi Matsuoka
- & Pablo A. Iglesias
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Article
| Open AccessDynamic interactions between E-cadherin and Ankyrin-G mediate epithelial cell polarity maintenance
The maintenance of cell polarity depends on adhesion complexes that tether to the cytoskeleton. Here the authors show the dynamic nature of E-cadherin–Ankyrin-G complex formation and investigate its functional role in epithelial cell polarity maintenance.
- Chao Kong
- , Xiaozhan Qu
- & Chao Wang
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Article
| Open AccessRedundancy and the role of protein copy numbers in the cell polarization machinery of budding yeast
Cell polarization of budding yeast recovers reliably and reproducibly from loss of one of its key components. Here, the authors show how this robustness emerges from redundant self-organization mechanisms coexisting within the underlying protein network.
- Fridtjof Brauns
- , Leila Iñigo de la Cruz
- & Erwin Frey
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Article
| Open AccessEpithelial plasticity and innate immune activation promote lung tissue remodeling following respiratory viral infection
After respiratory viral infection and in fibrotic lung disease, repair and remodeling processes particularly affect airway basal cell (BC) and alveolar epithelial cell populations. Here, using single cell transcriptomics and lineage tracing, the authors characterize this process and define roles for innate immune activation in the regulation of BC fate and alveolar remodeling.
- Andrew K. Beppu
- , Juanjuan Zhao
- & Barry R. Stripp
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Article
| Open AccessMolecular basis and design principles of switchable front-rear polarity and directional migration in Myxococcus xanthus
Cell polarity is key to many processes in bacteria. By focusing on the roadblock domain protein MglC, the authors elucidate the mechanistic basis and design principles of a system that spatiotemporally regulates switchable front-rear polarity and directional migration.
- Luís António Menezes Carreira
- , Dobromir Szadkowski
- & Lotte Søgaard-Andersen
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| Open AccessDirectionality of developing skeletal muscles is set by mechanical forces
The mechanisms that drive myocyte orientation and fusion to control muscle directionality are not well understood. Here authors show that the developing skeleton produces mechanical tension that instructs the directional outgrowth of skeletal muscles.
- Kazunori Sunadome
- , Alek G. Erickson
- & Igor Adameyko
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Article
| Open AccessCellular mechanisms of heterogeneity in NF2-mutant schwannoma
Schwannomas are mainly caused by NF2 tumour suppressor inactivation, but they display intratumoural heterogeneity. Here the authors show that this heterogeneity is caused by the loss of polarity and acquisition of different programmes of ErbB ligand production in NF2-mutant Schwann cells.
- Christine Chiasson-MacKenzie
- , Jeremie Vitte
- & Andrea I. McClatchey
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Article
| Open AccessActin polymerisation and crosslinking drive left-right asymmetry in single cell and cell collectives
In this work, the authors identify regulators of actin filament assembly involved in chiral organisation of the actin cytoskeleton in single cells and chiral alignment of cells in groups. This provides insights into how actin-driven chirality underlies tissue and organ asymmetry.
- Yee Han Tee
- , Wei Jia Goh
- & Alexander D. Bershadsky
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| Open AccessDirect Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein
SARS-CoV-2 infection can cause coagulopathic events. Kuhn et al. show by cryo-ET how the Spike protein impacts platelet morphology by binding to the platelet surface, leading to micro-activation; and investigate integrin as possible point of contact.
- Christopher Cyrus Kuhn
- , Nirakar Basnet
- & Naoko Mizuno
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Article
| Open AccessAnnexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis
Regulation of oriented cell divisions during development is important to position daughter cells and build a structured and functional tissue. Here the authors show that Annexin A1 is a key polarity protein that regulates planar orientation of the cell division axis to guide mammary epithelial morphogenesis.
- Maria Fankhaenel
- , Farahnaz S. Golestan Hashemi
- & Salah Elias
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Article
| Open AccessGlucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease
In polycystic kidney disease (PKD), fluid-filled cysts arise from tubules. Here the authors show that subjecting organoids to fluid shear stress in a PKD-on-a-chip microphysiological system promotes cyst expansion via an absorptive pathway.
- Sienna R. Li
- , Ramila E. Gulieva
- & Benjamin S. Freedman
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Article
| Open AccessPhase separation modulates the assembly and dynamics of a polarity-related scaffold-signaling hub
The polarization of distinct scaffold-signaling hubs at opposite cell poles constitutes the basis of asymmetric cell division. Here, the authors show that phase separation serves as a general mechanism to regulate the assembly and dynamics of a new-pole scaffold-signaling hub.
- Wei Tan
- , Sihua Cheng
- & Wei Zhao
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Article
| Open AccessSubcellular spatial transcriptomics identifies three mechanistically different classes of localizing RNAs
In this study the authors identify localized RNAs in the Drosophila follicular epithelium by spatial transcriptomics and through genetic analyses determine canonical and translation-based mechanisms underlying basal and apical RNA localization.
- Lucia Cassella
- & Anne Ephrussi
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Article
| Open AccessPolarized NHE1 and SWELL1 regulate migration direction, efficiency and metastasis
Cell migration regulates diverse (patho)physiological processes, including cancer metastasis. Here the authors show that the chloride ion channel SWELL1 and the ion exchanger NHE1 are preferentially enriched at the trailing and leading edges, respectively, of migrating cells and regulate cell volume to propel confined cells, favouring breast cancer cell extravasation and metastasis.
- Yuqi Zhang
- , Yizeng Li
- & Konstantinos Konstantopoulos
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Article
| Open AccessLive imaging and conditional disruption of native PCP activity using endogenously tagged zebrafish sfGFP-Vangl2
Planar cell polarity (PCP) is critical for tissue-wide coordination and successful development. Here Jussila et al. generate a GFP-Vangl2 fusion for live imaging and discover a surprising directionality to the intercellular propagation of cell polarity, and ultimately link PCP defects with idiopathic scoliosis.
- Maria Jussila
- , Curtis W. Boswell
- & Brian Ciruna
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Article
| Open AccessUbiquitination of CLIP-170 family protein restrains polarized growth upon DNA replication stress
The microtubule plus-end tracking protein Tip1 regulates microtubule dynamics and polar growth in fission yeast. Here the authors link the ubiquitination of Tip1 by ubiquitin ligase Dma1 to polarized growth inhibition upon DNA replication stress.
- Xi Wang
- , Fan Zheng
- & Quan-wen Jin
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Article
| Open AccessRab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
The promiscuous GTPase Rab35 has been shown to be involved in many important cellular functions. In this article, Francis et al. illustrate how Rab35 acts as a critical brake to actin remodeling during sprouting angiogenesis and how it is necessary for proper blood vessel development.
- Caitlin R. Francis
- , Hayle Kincross
- & Erich J. Kushner
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Article
| Open AccessAfadin couples RAS GTPases to the polarity rheostat Scribble
Goudreault et al. investigate the role of Afadin downstream of RAS GTPases, substantiating this cell adhesion protein as a true RAS effector that couples its activation to cell polarity through the Scribble protein.
- Marilyn Goudreault
- , Valérie Gagné
- & Matthew J. Smith
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Article
| Open AccessSynaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis
How pancreatic islets of Langerhans are built during development is incompletely understood. Here the authors find that Synaptotagmin-13 mediates remodeling of cell-matrix adhesion to regulate endocrine cell egression and islet morphogenesis.
- Mostafa Bakhti
- , Aimée Bastidas-Ponce
- & Heiko Lickert
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Article
| Open AccessRNA supply drives physiological granule assembly in neurons
RNA granules are important regulators of RNA metabolism. Here the authors report that RNA granules containing RNA helicase DDX6 disassemble during neuronal maturation.
- Karl E. Bauer
- , Niklas Bargenda
- & Michael A. Kiebler
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Article
| Open AccessCortical Cyclin A controls spindle orientation during asymmetric cell divisions in Drosophila
The Frizzled/Dishevelled planar cell polarity pathway is involved in mitotic spindle orientation, but how this is coordinated with the cell cycle is unclear. Here, the authors show with Drosophila sensory organ precursor cells that Cyclin A is recruited in prophase by Frizzled/Dishevelled, regulating division orientation.
- Pénélope Darnat
- , Angélique Burg
- & Agnès Audibert
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Article
| Open AccessSimultaneous stabilization of actin cytoskeleton in multiple nephron-specific cells protects the kidney from diverse injury
A common cellular manifestation for diverse kidney diseases is dysregulated actin cytoskeleton in distinct cell types that include glomerular podocytes and tubular epithelial cells. Here, authors pharmacologically activate dynamin and this results in polymerization and crosslinking of actin filaments to establish the structural integrity of these cells, thus ameliorating disease phenotypes.
- Kamalika Mukherjee
- , Changkyu Gu
- & Sanja Sever
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Article
| Open AccessASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis
The early embryo maintains its structure in the face of large mechanical stresses during morphogenesis. Here they show that ASPP2 acts to preserve epithelial integrity in regions of high apical tension during early development.
- Christophe Royer
- , Elizabeth Sandham
- & Shankar Srinivas
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Article
| Open AccessDistinct mechanisms orchestrate the contra-polarity of IRK and KOIN, two LRR-receptor-kinases controlling root cell division
Protein polarization coordinates many plant developmental processes. Here the authors show that IRK and KOIN, two LRR-receptor-kinases polarized to opposite sides of cells in the root meristem, rely on distinct mechanisms to achieve polarity.
- Cecilia Rodriguez-Furlan
- , Roya Campos
- & Jaimie M. Van Norman
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Article
| Open AccessDirectional reorientation of migrating neutrophils is limited by suppression of receptor input signaling at the cell rear through myosin II activity
Neutrophils migrate with remarkably stable front-rear polarization. Using optogenetic receptor control to induce reversal of polarization in restrictive microfluidic channels, the authors find that myosin II promotes this stability by suppressing transmission of receptor inputs at the cell rear.
- Amalia Hadjitheodorou
- , George R. R. Bell
- & Julie A. Theriot
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Article
| Open AccessNeuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins
Ribosomes, assembled in the nucleus and perinuclear region, are thought to remain invariant throughout their lifetime. Here the authors document the dynamic association or exchange of ribosomal proteins within mature ribosomes of neuronal cells.
- Claudia M. Fusco
- , Kristina Desch
- & Erin M. Schuman
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Article
| Open AccessReconstructing aspects of human embryogenesis with pluripotent stem cells
Human early development remains largely inaccessible, owing to technical and ethical limitations of working with natural embryos. Here the authors assess the extent to which human expanded pluripotent stem cells can specify distinct cell lineages and capture aspects of early human embryogenesis.
- Berna Sozen
- , Victoria Jorgensen
- & Magdalena Zernicka-Goetz
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Article
| Open AccessProximity proteomics identifies PAK4 as a component of Afadin–Nectin junctions
PAK4 is a kinase involved in cell-cell junctions, though the identify of the local protein network involving PAK4 is unclear. Here, the authors performed proximity proteomic analysis on mammalian PAK4 and find that PAK4 is associated with Afadin-dependent junctions, and report putative PAK4 phosphorylation substrates at this site.
- Yohendran Baskaran
- , Felicia Pei-Ling Tay
- & Edward Manser
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Article
| Open AccessCD13 orients the apical-basal polarity axis necessary for lumen formation
Epithelial cells that organise into structures that contain a lumen are polarised. Here, the authors show that the short intracellular domain of transmembrane protein CD13 is required to capture endosomes at the apical site and is required for the polarisation of cells.
- Li-Ting Wang
- , Abira Rajah
- & Luke McCaffrey
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Article
| Open AccessSpatio-temporal mRNA tracking in the early zebrafish embryo
Early stages of embryogenesis are known to depend on subcellular localization and transport of maternal mRNA, but systematic analyses have been hindered by a lack of methods for tracking of RNA. Here the authors combine spatially-resolved transcriptomics and single-cell RNA labeling to perform a spatio-temporal analysis of the transcriptome during early zebrafish development, revealing insights into this process.
- Karoline Holler
- , Anika Neuschulz
- & Jan Philipp Junker
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Article
| Open AccessEMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia
Sensory hair cells develop an asymmetric architecture to restrict stimulus detection to a single axis. Here the authors identify GPR156 as directing a 180-degree reversal in hair cell orientation through Gαi, downstream of EMX2 in the mouse inner ear and zebrafish lateral line.
- Katie S. Kindt
- , Anil Akturk
- & Basile Tarchini
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Article
| Open AccessAn ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism
The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive responses occur is unclear. Here, the authors show that alternate isoforms of the ARF GTPase exchange factor IQSEC1 direct phosphoinositide metabolism to control this switch.
- Marisa Nacke
- , Emma Sandilands
- & David M. Bryant
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Article
| Open AccessConstruction of intracellular asymmetry and asymmetric division in Escherichia coli
Establishing protein gradients for asymmetric cell division is fundamental across all kingdoms of life. Here the authors construct asymmetric cell division in E. coli by localizing the expression of RNA polymerase using an orthogonal unipolar scaffold, and restricting diffusion of its products.
- Da-Wei Lin
- , Yang Liu
- & Hsiao-Chun Huang
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Article
| Open AccessFilopodia-based contact stimulation of cell migration drives tissue morphogenesis
Contact stimulation of migration drives tissue morphogenesis. Here the authors report that filopodia-based contact-dependent asymmetry of cell–matrix adhesion drives directional movement, whereas contractile actin cables contribute to the integrity of the migrating cell cluster in the myotubes of Drosophila developing testes.
- Maik C. Bischoff
- , Sebastian Lieb
- & Sven Bogdan
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Article
| Open AccessThe molecular dynamics of subdistal appendages in multi-ciliated cells
Cilia originate from a basal body and basal foot, but the precise molecular mechanisms of basal foot biogenesis are unclear. Here, the authors show that ANKS1A interacts with FOP to transform the subdistal appendages from an unpolarized structure to a polarized structure with a basal foot.
- Hyunchul Ryu
- , Haeryung Lee
- & Soochul Park
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Article
| Open AccessStable inheritance of Sinorhizobium meliloti cell growth polarity requires an FtsN-like protein and an amidase
In Sinorhizobium bacteria, cell elongation takes place only at new cell poles, generated by cell division. Here, Krol et al. show that an FtsN-like protein and a peptidoglycan amidase are crucial for reliable selection of the new cell pole as cell elongation zone.
- Elizaveta Krol
- , Lisa Stuckenschneider
- & Anke Becker
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Article
| Open AccessBasement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue
The molecular mechanisms regulating macrophage recruitment to tumors are unclear. Here, the authors use a Drosophila overgrowth model to show how damaged basement membranes recruit macrophages to undead tissue, via an interdependent effect of reactive oxygen species and matrix metalloproteinase 2.
- Neha Diwanji
- & Andreas Bergmann
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Article
| Open AccessIRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules
The I-BAR protein IRSp53 senses membrane curvature but its physiological role is unclear. Here, the authors show that during early lumen morphogenesis, IRSp53 controls the shape of the apical plasma membrane and polarized trafficking and ensures the correct epithelial tubular architecture and if deleted, affects renal tubules morphogenesis in various organisms.
- Sara Bisi
- , Stefano Marchesi
- & Andrea Disanza
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Article
| Open AccessCoupling of melanocyte signaling and mechanics by caveolae is required for human skin pigmentation
Caveolae are plasma membrane invaginations playing crucial functions, like signal transduction and mechanoprotection. Here, the authors show that caveolae contribute to skin pigmentation by integrating the biochemical and mechanical response of epidermal melanocytes to extracellular cues.
- Lia Domingues
- , Ilse Hurbain
- & Cédric Delevoye
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Article
| Open AccessCell size sets the diameter of the budding yeast contractile ring
Budding yeast cell polarization is known to self-assemble, but it is still not clear what controls the size of the resulting septin ring. Here the authors show that the septin ring diameter is set by cell volume, ensuring that larger cells have larger rings.
- I. V. Kukhtevich
- , N. Lohrberg
- & K. M. Schmoller
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Article
| Open AccessSpitzenkörper assembly mechanisms reveal conserved features of fungal and metazoan polarity scaffolds
The Spitzenkörper (SPK) is a polarized accumulation of proteins and secretory vesicles associated with tip growth of fungal hyphae. Here, Zheng et al. study SPK assembly and dynamics, identify SPK protein scaffolds and associated proteins, and reveal similarities with other scaffolds from metazoans.
- Peng Zheng
- , Tu Anh Nguyen
- & Gregory Jedd
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Article
| Open AccessPar complex cluster formation mediated by phase separation
The evolutionarily conserved complex, the Par proteins, regulates cell polarity. Here, the authors show that in Drosophila neuroblasts, the Par complex exhibits liquid–liquid phase separation dependent on the cell cycle.
- Ziheng Liu
- , Ying Yang
- & Wenyu Wen
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Article
| Open AccessRole of the nuclear membrane protein Emerin in front-rear polarity of the nucleus
During cell migration, cells are polarized with distinct front vs. rear regions but whether and how polarity is transmitted to the nucleus is unclear. Here the authors show that frontally-biased endoplasmic reticulum and the nuclear membrane protein Emerin contribute to front-rear nuclear cell polarity.
- Paulina Nastały
- , Divya Purushothaman
- & Paolo Maiuri
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Article
| Open AccessStem cell-derived polarized hepatocytes
To model hepatocyte function accurately in vitro, it is necessary to generate and maintain a polarized epithelium. Here, the authors describe a protocol to generate polarized human pluripotent stem cell-derived hepatocyte-like cells (HLCs) to model enteric virus production and drug secretion in vitro.
- Viet Loan Dao Thi
- , Xianfang Wu
- & Charles M. Rice
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Article
| Open AccessDigenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome
While biallelic mutations of the SLC26A4 gene cause non-syndromic hearing loss with enlarged vestibular aqueducts or Pendred syndrome, a considerable number of patients carry mono-allelic mutations. Here the authors identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4.
- Mengnan Li
- , Shin-ya Nishio
- & Masanori Nakayama
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Article
| Open AccessCytokinetic bridge triggers de novo lumen formation in vivo
De novo lumen formation during vertebrate left–right organizer development is required for body axis establishment. Here the authors utilize zebrafish to demonstrate that the position and cleavage of the cytokinetic bridge in dividing left-right organizer cells dictates tissue morphogenesis.
- L. I. Rathbun
- , E. G. Colicino
- & H. Hehnly