title: Mechano-logical model of C. elegans germ line suggests feedback on the cell cycle.
abstract: The Caenorhabditis elegans germ line is an outstanding model system in which to study the control of cell division and differentiation. Although many of the molecules that regulate germ cell proliferation and fate decisions have been identified, how these signals interact with cellular dynamics and physical forces within the gonad remains poorly understood. We therefore developed a dynamic, 3D in silico model of the C. elegans germ line, incorporating both the mechanical interactions between cells and the decision-making processes within cells. Our model successfully reproduces key features of the germ line during development and adulthood, including a reasonable ovulation rate, correct sperm count, and appropriate organization of the germ line into stably maintained zones. The model highlights a previously overlooked way in which germ cell pressure may influence gonadogenesis, and also predicts that adult germ cells might be subject to mechanical feedback on the cell cycle akin to contact inhibition. We provide experimental data consistent with the latter hypothesis. Finally, we present cell trajectories and ancestry recorded over the course of a simulation. The novel approaches and software described here link mechanics and cellular decision-making, and are applicable to modeling other developmental and stem cell systems.
authors.affiliation: Computational Biology Group, Department of Computer Science, University of Oxford, Oxford OX1 3QD, UK Biological Computation Group, Computational Science Laboratory, Microsoft Research Cambridge, Cambridge CB1 2FB, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Atwell
authors.affiliation: Skirball Institute of Biomolecular Medicine, Department of Cell Biology and Kimmel Center for Stem Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Computational Biology Group, Department of Computer Science, University of Oxford, Oxford OX1 3QD, UK.
authors.forename: David
authors.initials: D
authors.lastname: Gavaghan
authors.affiliation: Biological Computation Group, Computational Science Laboratory, Microsoft Research Cambridge, Cambridge CB1 2FB, UK Faculty of Engineering, Bar-Ilan University, Ramat Gan 5290002, Israel.
authors.forename: Hillel
authors.initials: H
authors.lastname: Kugler
authors.affiliation: Skirball Institute of Biomolecular Medicine, Department of Cell Biology and Kimmel Center for Stem Cell Biology, New York University School of Medicine, New York, NY 10016, USA jane.hubbard@med.nyu.edu jmosborne@unimelb.edu.au.
authors.forename: E Jane Albert
authors.initials: EJ
authors.lastname: Hubbard
authors.affiliation: Computational Biology Group, Department of Computer Science, University of Oxford, Oxford OX1 3QD, UK Biological Computation Group, Computational Science Laboratory, Microsoft Research Cambridge, Cambridge CB1 2FB, UK School of Mathematics and Statistics, University of Melbourne, Melbourne 3010, Australia jane.hubbard@med.nyu.edu jmosborne@unimelb.edu.au.
authors.forename: James M
authors.initials: JM
authors.lastname: Osborne
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D017173:Caenorhabditis elegans / Q000235:genetics*; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D003198:Computer Simulation; D025461:Feedback, Physiological / Q000502:physiology*; D005854:Germ Cells / Q000166:cytology* / Q000502:physiology; D008954:Models, Biological; D012984:Software
keywords: C. elegans; Contact inhibition; Germ line; Mechanics; Modeling; Stem cell