A computational clonal analysis of the developing mouse limb bud
| Autor: | Miguel Torres, Carlos G. Arques, Luciano Marcon, James Sharpe |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Models
Anatomic Lineage (genetic) Limb Buds Ratolins (Animals de laboratori) Organogenesis Population Morphogenesis Computational biology Biology Models Biological Clonal analysis Developmental Biology/Pattern Formation Mice Cellular and Molecular Neuroscience Limb bud Cell Movement Genetics Animals Limb development Computer Simulation education lcsh:QH301-705.5 Molecular Biology Ecology Evolution Behavior and Systematics Body Patterning Developmental Biology/Organogenesis Homeodomain Proteins education.field_of_study Computational Biology/Systems Biology Ecology Developmental Biology/Morphogenesis and Cell Biology Clonatge Computational Biology Gene Expression Regulation Developmental Dimensional modeling Clone Cells Mice Inbred C57BL lcsh:Biology (General) Computational Theory and Mathematics Modeling and Simulation Developmental Biology/Cell Differentiation Developmental biology Research Article Transcription Factors |
| Zdroj: | PLoS Computational Biology, Vol 7, Iss 2, p e1001071 (2011) Recercat. Dipósit de la Recerca de Catalunya instname PLoS Computational Biology |
| Popis: | A comprehensive spatio-temporal description of the tissue movements underlying organogenesis would be an extremely useful resource to developmental biology. Clonal analysis and fate mappings are popular experiments to study tissue movement during morphogenesis. Such experiments allow cell populations to be labeled at an early stage of development and to follow their spatial evolution over time. However, disentangling the cumulative effects of the multiple events responsible for the expansion of the labeled cell population is not always straightforward. To overcome this problem, we develop a novel computational method that combines accurate quantification of 2D limb bud morphologies and growth modeling to analyze mouse clonal data of early limb development. Firstly, we explore various tissue movements that match experimental limb bud shape changes. Secondly, by comparing computational clones with newly generated mouse clonal data we are able to choose and characterize the tissue movement map that better matches experimental data. Our computational analysis produces for the first time a two dimensional model of limb growth based on experimental data that can be used to better characterize limb tissue movement in space and time. The model shows that the distribution and shapes of clones can be described as a combination of anisotropic growth with isotropic cell mixing, without the need for lineage compartmentalization along the AP and PD axis. Lastly, we show that this comprehensive description can be used to reassess spatio-temporal gene regulations taking tissue movement into account and to investigate PD patterning hypothesis. Author Summary A comprehensive mathematical description of the growth of an organ can be given by the velocity vectors defining the displacement of each tissue point in a fixed coordinate system plus a description of the degree of mixing between the cells. As an alternative to live imaging, a way to estimate the collection of such velocity vectors, known as velocity vector field, is to use cell-labeling experiments. However, this approach can be applied only when the labeled populations have been grown for small periods of time and the tensors of the velocity vector field can be estimated directly from the shape of the labeled population. Unfortunately, most of the available cell-labeling experiments of developmental systems have been generated considering a long clone expansion time that is more suitable for lineaging studies than for estimating velocity vector fields. In this study we present a new computational method that allows us to estimate the velocity vector field of limb tissue movement by using clonal data with long harvesting time and a sequence of experimental limb morphologies. The method results in the first realistic 2D model of limb outgrowth and establishes a powerful framework for numerical simulations of limb development. |
| Databáze: | OpenAIRE |
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