News & Views |
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Low-input lipidomics reveals lipid metabolism remodelling during early mammalian embryo development
Using low-input lipidomics in mouse and human embryos, Zhang, Shui, Li and colleagues find that lipid unsaturation increases with development towards the blastocyst stage. They further show that lipid desaturases contribute to successful embryo implantation.
- Ling Zhang
- , Jing Zhao
- & Jin Zhang
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Article |
Basal stem cell progeny establish their apical surface in a junctional niche during turnover of an adult barrier epithelium
Galenza et al. show that basal stem cell progeny seamlessly integrate into a physiologically active barrier epithelium by gestating their future apical surface in a sheltering niche created by a transient occluding junction.
- Anthony Galenza
- , Paola Moreno-Roman
- & Lucy Erin O’Brien
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Article |
Spatiotemporal dynamics of membrane surface charge regulates cell polarity and migration
Banerjee et al. detail the spatial and temporal dynamics of the surface charge on the inner leaflet of the plasma membrane and show that these dynamics are necessary and sufficient to regulate signalling pathways mediating cell migration and polarity.
- Tatsat Banerjee
- , Debojyoti Biswas
- & Peter N. Devreotes
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Article |
A monoastral mitotic spindle determines lineage fate and position in the mouse embryo
Pomp et al. show that specification of inner cell mass versus trophectoderm depends on a monoastral spindle that drives asymmetric cell division patterns, arguing against a stochastic inner–outer lineage segregation in the mouse embryo.
- Oz Pomp
- , Hui Yi Grace Lim
- & Nicolas Plachta
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Article |
Cell fate coordinates mechano-osmotic forces in intestinal crypt formation
Yang, Xue et al. demonstrate in intestinal organoids that region-specific cell fates drive actomyosin patterns and modulate luminal osmotic forces to coordinate morphogenesis.
- Qiutan Yang
- , Shi-Lei Xue
- & Prisca Liberali
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Article |
FERARI is required for Rab11-dependent endocytic recycling
Solinger et al. show that FERARI is a conserved tethering platform that mediates Rab11-dependent recycling at sorting endosomes.
- Jachen A. Solinger
- , Harun-Or Rashid
- & Anne Spang
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News & Views |
Endfoot regrowth for neural stem cell renewal
Tangential expansion of neural stem cells in the mammalian neocortex increases the number of cortical columns. A new study shows that neural stem cells that become detached from the apical surface during division regenerate an apical endfoot to ensure tangential expansion in the early stage but later lose this ability when radial expansion occurs.
- Masafumi Tsuboi
- & Yukiko Gotoh
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Article |
Endfoot regeneration restricts radial glial state and prevents translocation into the outer subventricular zone in early mammalian brain development
Fujita et al. show that endfoot regeneration of radial glia cells after division retains them in the ventricular zone in early development, independently of spindle orientation, but is lost during late neurogenesis.
- Ikumi Fujita
- , Atsunori Shitamukai
- & Fumio Matsuzaki
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News & Views |
Epithelial polarity limits EMT
Epithelial–mesenchymal transition (EMT) is crucial for development, and for dissemination and invasion of cancer cells. A study now identifies the apical–basolateral polarity status of epithelia as a checkpoint for EMT induction and tumour metastasis through aPKC–Par3-regulated degradation of the EMT transcription factor SNAI1.
- Oana-Diana Persa
- & Carien M. Niessen
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Article |
Apical–basal polarity inhibits epithelial–mesenchymal transition and tumour metastasis by PAR-complex-mediated SNAI1 degradation
Jung et al. demonstrate, using 3D organoid cultures, that the PAR–aPKC polarity complex counteracts epithelial–mesenchymal transition and invasion through phosphorylation-dependent regulation of SNAI1 stability.
- Hae-Yun Jung
- , Laurent Fattet
- & Jing Yang
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Review Article |
Mesenchymal–epithelial transition in development and reprogramming
This Review discusses the mesenchymal–epithelial transition and its roles in development, cellular fate conversions and somatic cell reprogramming.
- Duanqing Pei
- , Xiaodong Shu
- & Jean Paul Thiery
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Article |
Sequential formation and resolution of multiple rosettes drive embryo remodelling after implantation
Using time-lapse microscopy and transcriptome analysis of the post-implantation mouse embryo, Christodoulou et al. show that cavity fusion occurs through the formation and polarized resolution of multiple, multicellular three-dimensional rosettes.
- Neophytos Christodoulou
- , Christos Kyprianou
- & Magdalena Zernicka-Goetz
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Turning Points |
Having it all, a scientific career and a family
Sandrine Etienne-Manneville investigates the molecular mechanisms underlying cell migration in health and disease. She is Head of the Cell Polarity, Migration and Cancer laboratory, Director of the CNRS UMR3691 unit at the Institut Pasteur, Paris, France, a professor of cell biology and a mother of four.
- Sandrine Etienne-Manneville
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Article |
Counter-rotational cell flows drive morphological and cell fate asymmetries in mammalian hair follicles
Cetera et al. show that hair follicle development is characterised by counter-rotational cell rearrangements, which depend on myosin and Shh signalling, and direct cell fate asymmetry.
- Maureen Cetera
- , Liliya Leybova
- & Danelle Devenport
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Article |
Daughter-cell-specific modulation of nuclear pore complexes controls cell cycle entry during asymmetric division
Kumar et al. discover a pathway that regulates asymmetric cell cycle entry in budding yeast through Hos3-mediated deacetylation of nucleoporins in daughter cells, which affects the localization of the cell cycle regulators Whi5 and Cln2.
- Arun Kumar
- , Priyanka Sharma
- & Manuel Mendoza
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News & Views |
Optical control of cytoplasmic flows
Cytoplasmic flows are essential for various cellular processes. However, tools to manipulate these flows within cells are still lacking. Now research shows that an optical tool allows for control of cytoplasmic flows and can be used as a subcellular rheometer.
- Karsten Kruse
- , Nicolas Chiaruttini
- & Aurélien Roux
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Article |
Tumour spheres with inverted polarity drive the formation of peritoneal metastases in patients with hypermethylated colorectal carcinomas
Zajac et al. show that in colorectal cancer, decreased TGF-β signalling promotes apical actomyosin contractility and collective apical budding of invading tumour spheres with inverted polarity that drive metastatic spread.
- Olivier Zajac
- , Joel Raingeaud
- & Fanny Jaulin
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Technical Report |
Non-invasive perturbations of intracellular flow reveal physical principles of cell organization
Mittasch et al. show that controlling cytoplasmic flow via focused-light-induced cytoplasmic streaming (FLUCS), a non-invasive technique, can be used to invert asymmetric cell division in Caenorhabditis elegans zygotes.
- Matthäus Mittasch
- , Peter Gross
- & Moritz Kreysing
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Article |
Class III phosphatidylinositol-3-OH kinase controls epithelial integrity through endosomal LKB1 regulation
O’Farrell et al. show that class III PI3K regulates epithelial integrity through endosomal LKB1. Class III PI3K inactivation dysregulates LKB1 to alter cell polarity, and the PtdIns3P effector WDFY2 regulates LKB1.
- Fergal O’Farrell
- , Viola Hélène Lobert
- & Tor Erik Rusten
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Article |
EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity
In the developing mouse pancreas, EGFR regulates apical polarity via PI(3)K and Rac1 and elicits different ligand-dependent effects: BTC enables β-cell commitment and EGF inhibits polarization of epithelial progenitors during the primary transition.
- Zarah M. Löf-Öhlin
- , Pia Nyeng
- & Henrik Semb
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Article |
An apical MRCK-driven morphogenetic pathway controls epithelial polarity
Zihni et al. discover a role for Cdc42–MRCK signalling in establishing contractility at the apical pole, which in turn controls epithelial polarity in mammalian cells and Drosophila photoreceptors.
- Ceniz Zihni
- , Evi Vlassaks
- & Karl Matter
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Letter |
Cortical forces and CDC-42 control clustering of PAR proteins for Caenorhabditis elegans embryonic polarization
Studying polarity establishment in C. elegans zygotes, Wang et al. find, by imaging GFP-tagged proteins, that clusters of the PAR-3 polarity protein assemble in response to membrane tension created by actomyosin contractility.
- Shyi-Chyi Wang
- , Tricia Yu Feng Low
- & Fumio Motegi
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News & Views |
Getting a grip on collective cell migration
Many cell types in our body move in a collective manner, which requires individual cells to align their movements relative to that of their neighbours. A mechanism is now described in which cadherin-rich protrusions are extended from leading migrating cells and engulfed by follower cells to guide collective migration.
- Tamal Das
- & Joachim P. Spatz
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Article |
Engulfed cadherin fingers are polarized junctional structures between collectively migrating endothelial cells
Hayer et al. observe that collectively migrating endothelial cells extend rear VE-cadherin-rich membrane structures that are engulfed by follower cells, correlating spatially with the direction of movement.
- Arnold Hayer
- , Lin Shao
- & Tobias Meyer
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Letter |
An interaction between Scribble and the NADPH oxidase complex controls M1 macrophage polarization and function
Muthuswamy et al. report that in macrophages SCRIB interacts with the NADPH oxidase complex to promote the production of reactive oxygen species needed to kill bacteria. Conversely, loss of SCRIB promotes M1 macrophage polarization and inflammation.
- Weiyue Zheng
- , Masataka Umitsu
- & Senthil K. Muthuswamy
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Resource |
A combined binary interaction and phenotypic map of C. elegans cell polarity proteins
Boxem and colleagues perform a yeast two-hybrid screen to identify interactions between C. elegans polarity genes, followed by an RNAi screen to identify the functions of interaction pairs in the establishment and maintenance of cell polarity in various tissues.
- Thijs Koorman
- , Diana Klompstra
- & Mike Boxem
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Article |
A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors
Nerlov and colleagues show that expression of mKitL by cortical vascular endothelial cells is important for DN1 progenitor maintenance, whereas expression of mKitL by cortical thymic epithelial cells is required for maintaining DN2 progenitor cells.
- Mario Buono
- , Raffaella Facchini
- & Claus Nerlov
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Letter |
Transient junction anisotropies orient annular cell polarization in the Drosophila airway tubes
Samakovlis and colleagues perform a genome-wide, tissue-specific RNAi screen in the Drosophila larval and adult airway systems and find that an initial transient anisotropic distribution of aPKC drives fibre orientation during tube formation.
- Chie Hosono
- , Ryo Matsuda
- & Christos Samakovlis
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Article |
An instructive role for C. elegans E-cadherin in translating cell contact cues into cortical polarity
Nance and colleagues report that the E-cadherin HMR-1 recruits the RhoGAP PAC-1 to cell–cell contact and thereby drives symmetry breaking in C. elegans embryos.
- Diana Klompstra
- , Dorian C. Anderson
- & Jeremy Nance
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Article |
Wdr1-mediated cell shape dynamics and cortical tension are essential for epidermal planar cell polarity
Fuchs and colleagues report a role for the F-actin binding protein Wdr1 in the establishment of planar polarity in the mouse embryonic epidermis by mediating tension.
- Chen Luxenburg
- , Evan Heller
- & Elaine Fuchs
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Article |
Independent and coordinate trafficking of single Drosophila germ plasm mRNAs
Gavis and colleagues characterize RNP trafficking and assembly using quantitative single-molecule imaging and find mRNAs destined for the germ cells are assembled differently from oskar, the germline determinant mRNA.
- Shawn C. Little
- , Kristina S. Sinsimer
- & Elizabeth R. Gavis
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Article |
Cellular chirality arising from the self-organization of the actin cytoskeleton
Bershadsky and colleagues show that cells confined to circular adhesive patterns exhibit defined and dynamic self-assembly of their actin cytoskeleton into a chiral pattern with defined handedness, potentially informing left–right cell asymmetry.
- Yee Han Tee
- , Tom Shemesh
- & Alexander D. Bershadsky
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News & Views |
Merlin's wizardry guides cohesive migration
Cells often migrate in tightly connected groups with coordinated movement and polarity. The collective migration of epithelial cell sheets is now shown to be mediated by a signalling axis that involves the merlin tumour-suppressor protein, the tight-junction-associated angiomotin–Rich1 complex and the Rac1 small GTPase.
- Ansgar Zoch
- & Helen Morrison
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Article |
Developmental regulation of apical endocytosis controls epithelial patterning in vertebrate tubular organs
Bagnat, Martín-Belmonte and colleagues reveal that plasmolipin (PLLP) is upregulated in the zebrafish midgut during development and controls epithelial patterning by promoting polarized endocytosis.
- Alejo E. Rodríguez-Fraticelli
- , Jennifer Bagwell
- & Fernando Martín-Belmonte
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Article |
A molecular mechanotransduction pathway regulates collective migration of epithelial cells
Spatz and colleagues report that intercellular pulling forces between leader and follower cells in migrating epithelial sheets regulate merlin subcellular localization and the crosstalk between merlin and Rac1 to promote collective cell migration.
- Tamal Das
- , Kai Safferling
- & Joachim P. Spatz
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Letter |
FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear movement
Gundersen and colleagues report that the FHOD1 formin is involved in nuclear positioning, by physically linking nesprin-2G, a protein of the outer nuclear membrane, to actin cables, to allow the formation of the transmembrane actin-associated nuclear (TAN) lines that are needed to move the nucleus.
- Stefan Kutscheidt
- , Ruijun Zhu
- & Gregg G. Gundersen
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Uba1 functions in Atg7- and Atg3-independent autophagy
Autophagy, which is believed to be an Atg7- and Atg3-dependent process, is known to be involved in animal development. Baehrecke and colleagues show that autophagy drives the controlled degradation of the developing Drosophila midgut. Interestingly, this process is Atg7- and Atg3-independent, and instead requires the E1-activating enzyme Uba1 for programmed reduction of cell size in the midgut.
- Tsun-Kai Chang
- , Bhupendra V. Shravage
- & Eric H. Baehrecke
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Article |
Apical domain polarization localizes actin–myosin activity to drive ratchet-like apical constriction
Martin and colleagues analyse the mechanism underlying Twist- and Rho1-driven apical constriction of ventral furrow cells in Drosophila. They characterize the spatial localization of the Rho1 effectors Rok1 and Dia, and their effects on the actomyosin network and adherens junctions.
- Frank M. Mason
- , Michael Tworoger
- & Adam C. Martin
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News & Views |
Anthrax receptors position the spindle
Spindle orientation plays a pivotal role in tissue morphogenesis. An asymmetric anthrax receptor cap is revealed to promote activation of a formin to orient the spindle along the planar cell polarity (PCP) axis in zebrafish dorsal epiblast cells.
- Nicolas Minc
- & Matthieu Piel
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News & Views |
'Goldilocks' suppressor screen identifies web of polarity regulators
Genome sequencing and RNAi have been powerful allies in the quest to assign function to every gene. Systematic RNAi screens identify essential genes efficiently, but are less effective with pleiotropic or redundant genes. A common trick used by geneticists to overcome this problem is to screen for genetic interactors — mutations that enhance or suppress the phenotype of a starting mutation. Now, this classic approach has been combined with the versatility of RNAi to generate an expanded gene network for cell polarity.
- Geraldine Seydoux
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Article |
An integrin–ILK–microtubule network orients cell polarity and lumen formation in glandular epithelium
Mammary gland morphogenesis involves the polarization of epithelial cells and the formation of a lumen. Akhtar and Streuli demonstrate that β1 integrin and the downstream kinase ILK at the basement membrane are required for polarization in this system, through orientation of microtubules and Golgi positioning.
- Nasreen Akhtar
- & Charles H. Streuli
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Resource |
Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy
Cell polarity is important for the function of many animal cells, and several aspects of its establishment are conserved across species, from worm to human. Ahringer and colleagues have performed large-scale genetic interaction screens in Caenorhabditis elegans to identify a network of polarity regulators that includes genes not previously associated with polarity, such as the nuclear pore protein NPP-2.
- Bruno Thomas Fievet
- , Josana Rodriguez
- & Julie Ahringer
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Review Article |
Role of membrane traffic in the generation of epithelial cell asymmetry
Epithelial cells have an apical–basolateral axis of polarity, which is required for epithelial functions including barrier formation, vectorial ion transport and sensory perception. Here we review what is known about the sorting signals, machineries and pathways that maintain this asymmetry, and how polarity proteins interface with membrane-trafficking pathways to generate membrane domains de novo.It is becoming apparent that membrane traffic does not simply reinforce polarity, but is critical for the generation of cortical epithelial cell asymmetry.
- Gerard Apodaca
- , Luciana I. Gallo
- & David M. Bryant
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Article |
β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell–cell junctions by differentially regulating Tiam1 activity
Malliri and colleagues demonstrate that an apicobasal Rac activity gradient at cell–cell junctions is important for tight-junction assembly and establishment of apicobasal polarity. They show that this gradient is generated by the distinct spatial regulation of the Rac activator Tiam1 by β2-syntrophin and Par-3.
- Natalie A. Mack
- , Andrew P. Porter
- & Angeliki Malliri
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Article |
Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells
By performing a screen for genes that regulate epithelial architecture, Martín–Belmonte and colleagues identify key roles for the synaptotagmin-like proteins Slp2-a and Slp4-a in restricting lumen generation. They find that Slp2-a targets Rab27a/b-positive vesicles to PtdIns(4,5)P2-enriched apical membranes, whereas Slp4-a controls subsequent vesicle tethering and fusion. Their coordinated activities ensure the creation of a single lumen per cell.
- Manuel Gálvez-Santisteban
- , Alejo E. Rodriguez-Fraticelli
- & Fernando Martín-Belmonte
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Article |
Rap2A links intestinal cell polarity to brush border formation
Microvilli are essential for the function of intestinal cells. Bos and colleagues have found that the polarity kinase LKB-1 induces PtdIns(4,5)P2 enrichment at the apical membrane. This leads to the successive accumulation of phosphatidic acid and the small GTPase Rap2A with its GEF and its effectors. These, in turn, trigger the changes in the actin cytoskeleton responsible for microvilli formation.
- Martijn Gloerich
- , Jean Paul ten Klooster
- & Johannes L. Bos
Lipid remodelling in mammalian development