Content area
Full Text
About the Authors:
Silas Boye Nissen
Roles Data curation, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft, Writing - review & editing
Affiliation: StemPhys, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
Marta Perera
Roles Data curation, Investigation, Methodology, Visualization, Writing - review & editing
Affiliation: The Danish Stem Cell Centre, DanStem, University of Copenhagen, Copenhagen, Denmark
Javier Martin Gonzalez
Roles Investigation, Methodology, Supervision, Validation, Visualization
Affiliation: Transgenic Core Facility, University of Copenhagen, Copenhagen, Denmark
Sophie M. Morgani
Roles Conceptualization, Investigation, Methodology, Validation, Writing - review & editing
Affiliation: The Danish Stem Cell Centre, DanStem, University of Copenhagen, Copenhagen, Denmark
Mogens H. Jensen
Roles Conceptualization, Funding acquisition, Investigation, Methodology, Writing - review & editing
Affiliation: StemPhys, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
Kim Sneppen
Roles Conceptualization, Investigation, Methodology, Project administration, Supervision, Visualization, Writing - review & editing
Affiliation: CMOL, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
Joshua M. Brickman
Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing - review & editing
* E-mail: [email protected] (JMB); [email protected] (AT)
Affiliations StemPhys, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark, The Danish Stem Cell Centre, DanStem, University of Copenhagen, Copenhagen, Denmark
Ala Trusina
Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Software, Supervision, Visualization, Writing - review & editing
* E-mail: [email protected] (JMB); [email protected] (AT)
Affiliation: StemPhys, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
ORCID http://orcid.org/0000-0003-1945-454XAbstract
Early mammalian development is both highly regulative and self-organizing. It involves the interplay of cell position, predetermined gene regulatory networks, and environmental interactions to generate the physical arrangement of the blastocyst with precise timing. However, this process occurs in the absence of maternal information and in the presence of transcriptional stochasticity. How does the preimplantation embryo ensure robust, reproducible development in this context? It utilizes a versatile toolbox that includes complex intracellular networks coupled to cell-cell communication, segregation by differential adhesion, and apoptosis. Here, we ask whether a minimal set of developmental rules based on this toolbox is sufficient for successful blastocyst development, and to what extent these rules can explain mutant and experimental phenotypes. We implemented experimentally reported mechanisms for polarity, cell-cell signaling, adhesion, and apoptosis as a set of developmental rules in an agent-based in silico model of physically interacting cells....