Asymmetric division

Asymmetric division is crucial for generating cellular diversity during development and in stem cell lineages. For asymmetric division to be successful, the mitotic spindle must be positioned in a manner that ensures proper segregation of cytoplasmic constituents to daughter cells. In one-cell C. elegans embryos, the mitotic spindle is positionined eccentrically in response to anterior-posterior (A-P) polarity cues (Fig. 1).

Fig. 1 | One-cell stage C. elegans embryo in mitosis. Embryo stained with antibodies against α-tubulin, which highlights microtubules (green), the centrosomal protein TAC-1 (red, visible in yellow at spindle poles) and counterstained with a DNA dye (blue). Note astral microtubules extending from the spindle poles to the cell membrane.

Work performed in many laboratories, including ours, indicate that spindle positioning requires the function of an evolutionary conserved ternary complex consisting of a large coiled-coil protein, a GoLoCo domain containing protein, and a heterotrimeric G protein in the GDP-bound mode (Gönczy, 2008). The members of this ternary complex are LIN-5/GPR-1/2/Gα in C. elegans and NuMA/LGN/Gαi in H. sapiens. The available evidence indicates that the ternary complex anchors the minus end directed motor protein complex dynein at the cell cortex. Dynein is thought to generate pulling forces on astral microtubules that emanate from the spindle poles, thus positioning the mitotic spindle (see Fig. 2).

Fig. 2 | Working model for spindle positioning in human cells. The ternary complex comprising (NuMA/LGN/Gα) anchors the minus-end directed motor protein complex dynein at the cell cortex below the plasma membrane. Due to its motor activity, cortical dynein generates pulling forces by attempting to move on the astral microtubules (shown in red), which must depolymerize concommitantly, thus ensuring proper spindle positioning.

We found that dynein levels at the cell cortex must be tightly regulated for accurate metaphase spindle positioning, since an increase or a decrease in cortical dynein has drastic consequences on spindle positioning (Fig. 3) (Kotak et al.; 2012).

Fig. 3 | Overexpression of ternary complex component influence spindle positioning. (A) Overexpression of GPR-1 in C. elegans embryos influences spindle positioning as monitored by DIC microscopy. Time is indicated in minutes: seconds. Note increase in spindle movements (shown in red) in embryo overexpressing GPR-1 (YFP-GPR-1) compared to the wild-type. (B) Similarly, overexpression of the GPR-1/2 homolog LGN in human cells influences spindle positioning. DNA is shown in red and microtubules in green. Time is indicated in hours: minutes. Note drastic movement of metaphase plate (shown in red) in cells expressing YFP-LGN in comparison with control cells.

Our publications on this topic

S. G. S. Pai; Y. Reuland; I. F. C. Smith : Data-Interpretation Methodologies for Practical Asset-Management; Journal of Sensor and Actuator Networks. 2019-06-22. DOI : 10.3390/jsan8020036.
M. Izadi; E. Ghafoori; A. Hosseini; J. Michels; M. Motavalli : Strengthening of steel beams using iron-based shape memory alloy (Fe-SMA) strips. 2019-03. Towards a Resilient Built Environment - Risk and Asset Management, IABSE Symposium 2019 Guimarães, Guimarães, Portugal, March 27-29, 2019.
E. Ghafoori; A. Hosseini; R. Al-Mahaidi; X.-L. Zhao; M. Motavalli et al. : CFRP Strengthening and Long-Term Monitoring of an Old Metallic Roadway Bridge in Melbourne. 2019-03. Towards a Resilient Built Environment Risk and Asset Management, IABSE SYMPOSIUM GUIMARÃES 2019 , Guimarães, Portugal , March 27-29, 2019.
M. Badoux; M. Billing; H.-A. Klok : Polymer brush interfaces for protein biosensing prepared by surface-initiated controlled radical polymerization; Polymer Chemistry. 2019. DOI : 10.1039/C9PY00163H.
D. N. Arena / D. Kyritsis (Dir.) : Towards semantics-driven modelling and simulation of context-aware manufacturing systems. Lausanne, EPFL, 2019. DOI : 10.5075/epfl-thesis-7150.
M. Proverbio / I. Smith (Dir.) : Measurement data interpretation and prediction for optimal management of bridges. Lausanne, EPFL, 2019. DOI : 10.5075/epfl-thesis-7567.
S. Aguacil Moreno / E. Rey (Dir.) : Architectural Design Strategies for Building-Integrated Photovoltaics in residential building renovation processes. Lausanne, EPFL, 2019. DOI : 10.5075/epfl-thesis-9332.
J. A. Blatt / S. Malamud (Dir.) : Essays in Financial Economics. Lausanne, EPFL, 2019. DOI : 10.5075/epfl-thesis-9136.
C. M. Aouinait / D. Foray (Dir.) : Innovation capacity of the agricultural sector: network of productive interactions, knowledge transfer and differentiation mechanisms. Lausanne, EPFL, 2019. DOI : 10.5075/epfl-thesis-9116.
M. Razeghian; T. Weber : The Advent of the Sharing Culture and its Effect on Product Pricing; Electronic Commerce Research and Applications. 2019. DOI : 10.1016/j.elerap.2018.06.001.
F. Gallien; S. Kassibrakis; S. Malamud : Hedge or Rebalance: Optimal Risk Management with Transaction Costs; Risks. 2018-12-01. DOI : 10.3390/risks6040112.
I. F. C. Smith : Measurement data interpretation for sustainable asset management and for future responsive cities (Keynote talk) ; 8th International Conference of Tropical and Subtropical Green Building Council Alliance & 9th Cross-Strait Green Building Technology Development Forum, Hong Kong, November, 18-20, 2018.
A. Pagani; C. R. Binder : Agent-based modeling for studying the choices of households in Switzerland ; Swiss Inter- and Transdisciplinarity Day 2018, EPFL, Lausanne, 15.11.2018.
K. Christakou; A. Abur; M. Paolone : Voltage Control in Active Distribution Networks Under Uncertainty in the System Model: A Robust Optimization Approach; IEEE Transactions on Smart Grid. 2018-11-01. DOI : 10.1109/TSG.2017.2693212.
E. Namor / R. Cherkaoui (Dir.) : Advanced models and algorithms to provide multiple grid services with battery storage systems. EPFL, 2018-09-21.
F. Sossan; R. K. Gupta; E. Scolari; M. Paolone : Increasing the PV hosting Capacity of Distribution Grids with Distributed Storage: Siting, Sizing and Costs. 2018-09-03.
S. Malamud; G. Vilkov : Non-myopic betas; Journal of Financial Economics. 2018-08-01. DOI : 10.1016/j.jfineco.2018.05.004.
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A. Cherqui : Deep learning on graph for semantic segmentation of point cloud ; 2018-07-02.
D. Ackerer; D. Filipović; S. Pulido : The Jacobi stochastic volatility model; Finance and Stochastics. 2018-07-01. DOI : 10.1007/s00780-018-0364-8.
A. M. A. Elkady; S.-H. Hwang; D. Lignos : EaRL: Toolbox for Earthquake Risk and Loss Assessment of Building Assets. 2018-06-22. 16th European Conference on Earthquake Engineering, Thessaloniki, Greece, June 18-21, 2018.
I. F. C. Smith : Advanced measurement data interpretation for sustainable asset management (Keynote talk) ; ICCCBE, Tampere, Finland, June, 4-7, 2018.
H. Albrecher; D. Bauer; P. Embrechts; D. Filipović; P. Koch-Medina et al. : Asset-liability management for long-term insurance business; European Actuarial Journal. 2018-06-01. DOI : 10.1007/s13385-018-0167-5.
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I. F. C. Smith : Enhancing asset management with measurements. Carnegie Mellon University.
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I. F. C. Smith : An engineering approach to interpreting measurement data for asset management. Curtin University, Perth, Australia.
S. Pai : Data Interpretation for Asset Management. IITM, India.
M. Tamizifar : Development of a Monolithic Fiber-Based Electric Field Sensor ; 2018.
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J. Ciers; J. G. Roch; J. -F. Carlin; G. Jacopin; R. Butte et al. : Propagating Polaritons in III-Nitride Slab Waveguides; Physical Review Applied. 2017. DOI : 10.1103/PhysRevApplied.7.034019.
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G. Lilis; G. Conus; N. Asadi; M. Kayal : Towards the next generation of intelligent building: An assessment study of current automation and future IoT based systems with a proposal for transitional design; Sustainable Cities And Society. 2017. DOI : 10.1016/j.scs.2016.08.019.
G. Favara; E. Morellec; E. Schroth; P. Valta : Debt enforcement, investment, and risk taking across countries; Journal of Financial Economics. 2017. DOI : 10.1016/j.jfineco.2016.09.002.
G. Consigli; D. Kuhn; P. Brandimarte : Optimal Financial Decision Making Under Uncertainty; Optimal Financial Decision Making under Uncertainty; Springer International Publishing, 2017. p. 255-290.
A. M. Mezoued : Espace(s) public(s) d’Alger : les signaux faibles d’une reconstruction spatiale et d’une construction politique; Vivre ensemble; AIMF, 2016. p. 49-55.
H. Amini; D. Filipovic; A. Minca : To Fully Net or Not to Net: Adverse Effects of Partial Multilateral Netting; Operations Research. 2016. DOI : 10.1287/opre.2015.1414.
J. C. Jackwerth; A. Slavutskaya : The total benefit of alternative assets to pension fund portfolios; Journal Of Financial Markets. 2016. DOI : 10.1016/j.finmar.2016.06.002.
A. Mukherjee / L. Lambertini (Dir.) : Credit Supply and the Macroeconomy. Lausanne, EPFL, 2016. DOI : 10.5075/epfl-thesis-7371.
I. F. C. Smith : Studies of Sensor Data Interpretation for Asset Management of the Built Environment; Frontiers in Built Environment. 2016. DOI : 10.3389/fbuil.2016.00008.
M. J. D. Cambou / D. Filipovic; A. C. Davison (Dir.) : Essays on Capital Calculation in Insurance. Lausanne, EPFL, 2016. DOI : 10.5075/epfl-thesis-7269.
N. Rujeerapaiboon / D. Kuhn; W. Wiesemann (Dir.) : Dimensionality Reduction in Dynamic Optimization under Uncertainty. Lausanne, EPFL, 2016. DOI : 10.5075/epfl-thesis-7235.
P. Thalmann : Décarboniser la Suisse: Trop cher et inutile? ; Comment agir face à l'urgence climatique?, Lausanne, 1 novembre 2016.
S. Kotak; K. Afshar; C. Busso; P. Gönczy : Aurora A kinase regulates proper spindle positioning in C-elegans and in human cells; Journal Of Cell Science. 2016. DOI : 10.1242/jcs.184416.
P. U. Moser / R. Seifert (Dir.) : Supply Chain Management in Process Industries: Empirical Investigations for Commodity Markets. Lausanne, EPFL, 2016. DOI : 10.5075/epfl-thesis-7190.
R. P. Lebret / H. Bourlard; R. Collobert (Dir.) : Word Embeddings for Natural Language Processing. Lausanne, EPFL, 2016. DOI : 10.5075/epfl-thesis-7148.
G. Viscusi; C. Batini : Information Production and Social Value for Public Policy: A Conceptual Modeling Perspective; Policy & Internet. 2016. DOI : 10.1002/poi3.121.
S. Lufkin; E. Rey : Green Density. Interdisciplinary education and research project for the design of sustainable neighborhoods. 2016. PLEA 2016, Los Angeles, USA, July 11-13, 2016.
R. Lebret (Dir.) : Building Word Embeddings for Solving Natural Language Processing. École Polytechnique Fédérale de Lausanne, 2016.
J. Borrego-Pinto; K. Somogyi; M. A. Karreman; J. Koenig; T. Mueller-Reichert et al. : Distinct mechanisms eliminate mother and daughter centrioles in meiosis of starfish oocytes; Journal Of Cell Biology. 2016. DOI : 10.1083/jcb.201510083.
G. De Rassenfosse; T. Fischer : Venture Debt Financing: Determinants of the Lending Decision; Strategic Entrepreneurship Journal. 2016. DOI : 10.1002/sej.1220.
S. Aguacil Moreno; S. Lufkin; E. Rey : Architectural design scenarios with building-integrated photovoltaic solutions in renovation processes: Case study in Neuchâtel (Switzerland). 2016. PLEA2016 Los Angeles - 32nd International Conference on Passive and Low Energy Architecture, Los Angeles, California, USA, July 11-13, 2016.
S. Aguacil Moreno; S. Lufkin; E. Rey : Towards integrated design strategies for implementing BIPV systems into urban renewal processes: first case study in Neuchâtel (Switzerland) ; Sustainable Built Environment (SBE) regional conference, Zurich, Switzerland, June 15-17, 2016.
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M. Mura; M. Longo; L. Massa : Exploring the effects of intellectual capital architectures on organizational ambidexterity. An fsQCA approach. 2015. 10th International Forum on Knowledge Asset Dynamics (IFKAD), Bari, ITALY, JUN 10-12, 2015. p. 1001-1011.
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D. Filipovic; R. Kremslehner; A. Muermann : Optimal Investment and Premium Policies Under Risk Shifting and Solvency Regulation; Journal Of Risk And Insurance. 2015. DOI : 10.1111/jori.12021.
F. Belo; P. Collin-Dufresne; R. S. Goldstein : Dividend Dynamics and the Term Structure of Dividend Strips; Journal Of Finance. 2015. DOI : 10.1111/jofi.12242.
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T. Peters; J. Thiel; C. Tucci : Protecting Options in Global Markets: Evidence on the Use of Strategic Disclosure. 2015. 75th Annual Meeting of the Academy of Management, Vancouver, Canada, 7-11 August, 2015.
T. A. Männistö / M. Finger (Dir.) : Mitigating Crime Risks in the International Logistics Network. Lausanne, EPFL, 2015. DOI : 10.5075/epfl-thesis-6513.
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