Differentiation, cell sorting and proportion regulation in the slug stage of Dictyostelium discoideum |
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| Authors: | E F Pate H G Othmer |
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| Affiliation: | 1. Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK;2. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK;3. Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Forvie Site, Robinson Way, Cambridge CB2 0SR, UK;4. MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Wort’s Causeway, Cambridge CB1 8RN, UK;5. Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK;6. The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge, University of Cambridge, Strangeways Research Laboratory, Wort’s Causeway, Cambridge CB1 8RN, UK;7. Blood Research Group, NHS Blood and Transplant, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9BQ, UK;8. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK;9. Department of Haematology, Barts Health NHS Trust, The Royal London Hospital, Whitechapel Road, London, London E1 1BB, UK;10. Department of Molecular Biology, Radboud University, Faculty of Science, Nijmegen 6525GA, the Netherlands;11. Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0QQ, UK;12. National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge CB2 0QQ, UK;13. NIHR BioResource-Rare Diseases, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK;14. Département de Génétique et Développement (GEDEV), University of Geneva, 1211 Geneve 4, Switzerland;15. Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, 3000 Leuven, Belgium;16. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK;17. Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK;18. UK Biobank Ltd., 1-4 Spectrum Way, Adswood, Stockport SK3 0SA, UK;19. British Heart Foundation Centre of Excellence, Division of Cardiovascular Medicine, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK;20. Emma Children’s Hospital, Academic Medical Center (AMC), University of Amsterdam, Location H7-230, Meibergdreef 9, Amsterdam 1105AZ, the Netherlands;21. Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Plesmanlaan 125, Amsterdam, 1066CX, the Netherlands;22. Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029 Madrid, Spain;23. Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK;24. Human Genetics, McGill University, 740 Dr. Penfield, Montreal, QC H3A 0G1, Canada;25. Bioinformatics and Genomics, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Carrer del Dr. Aiguader, 88, Barcelona 8003, Spain;26. Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Plaça de la Mercè, 10- 12, Barcelona 8002, Spain;27. Computational Genomics, Institut Hospital del Mar d’Investigacions Mediques (IMIM), Carrer del Dr. Aiguader, 88, Barcelona 8003, Spain;28. UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK;29. Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK;30. Department of Haematology, Churchill Hospital, Headington, Oxford OX3 7LE, UK;1. Department of Automotive, Mechanical and Manufacturing Engineering, Faculty of Engineering and Applied Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, Ontario L1H 7K4, Canada;2. Faculty of Mechanical Engineering, Yildiz Technical University, Besiktas, Istanbul, Turkey;1. Phyto-technologies and Invasion Lab, Department of Environmental Science, School of Earth Sciences and Natural Resources Management, Mizoram University, Aizawl, Mizoram, India;2. Ecosystem Analysis Lab, Centre of Advanced Study in Botany, Banaras Hindu University (B.H.U.), Varanasi, 221005, India;1. Laboratory for Aviation and the Environment, Department of Aeronautics and Astronautics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA;2. United States Federal Aviation Administration, Office of Environment and Energy, AEE-1 800 Independence Ave SW Suite 900W, Washington, DC 20591, USA;3. Center for Environmental Sciences, Hasselt University, Campus Diepenbeek, Agoralaan Building D, 3590 Diepenbeek, Belgium;4. GasTOPs Inc., 1011 Polytek Street, Ottawa, ON, Canada K1J 9J3 |
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| Abstract: | Recent experimental work suggests that under normal conditions cell sorting plays an important part in maintaining and re-establishing the axial pattern of cell types in the slug stage of the cellular slime mold Dictyostelium discoideum. Following removal of the anterior zone of the slug, anterior-like cells that are normally distributed throughout the posterior of the slug rapidly migrate to the anterior end of the transected slug, and new anterior-like cells appear in the posterior portion. These results provide evidence that the direct linkage between spatial location and differentiation hypothesized in positional information models of spatial pattern formation is not universal. In this paper we develop and analyze a class of mathematical models of the slug in which cell determination can be less rigidly tied to spatial location, and which involve chemotactic cell sorting to re-establish and maintain the spatial pattern of cell types. We show that these models can reproduce the qualitative aspects of the experimental observations and that sorting takes place on the observed time scale when reasonable values of the parameters are used. |
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