A Multi-cell, Multi-scale Model of Vertebrate Segmentation and Somite Formation

Susan D Hester, Julio M Belmonte, J Scott Gens, Sherry G Clendenon and James A Glazier

PLOS Computational Biology, 2011, vol. 7, issue 10, 1-32

Abstract: Somitogenesis, the formation of the body's primary segmental structure common to all vertebrate development, requires coordination between biological mechanisms at several scales. Explaining how these mechanisms interact across scales and how events are coordinated in space and time is necessary for a complete understanding of somitogenesis and its evolutionary flexibility. So far, mechanisms of somitogenesis have been studied independently. To test the consistency, integrability and combined explanatory power of current prevailing hypotheses, we built an integrated clock-and-wavefront model including submodels of the intracellular segmentation clock, intercellular segmentation-clock coupling via Delta/Notch signaling, an FGF8 determination front, delayed differentiation, clock-wavefront readout, and differential-cell-cell-adhesion-driven cell sorting. We identify inconsistencies between existing submodels and gaps in the current understanding of somitogenesis mechanisms, and propose novel submodels and extensions of existing submodels where necessary. For reasonable initial conditions, 2D simulations of our model robustly generate spatially and temporally regular somites, realistic dynamic morphologies and spontaneous emergence of anterior-traveling stripes of Lfng. We show that these traveling stripes are pseudo-waves rather than true propagating waves. Our model is flexible enough to generate interspecies-like variation in somite size in response to changes in the PSM growth rate and segmentation-clock period, and in the number and width of Lfng stripes in response to changes in the PSM growth rate, segmentation-clock period and PSM length. Author Summary: Recent decades have seen a revolution in experimental techniques that has shifted the focus of experimental biology from behaviors at the micron (cell) scale to those at the nanometer (molecular) scale. An ever-increasing number of studies detail subcellular behaviors, genetic pathways and protein interactions that relate to specific cell functions. This progress, while welcome, sometimes leads us to forget that these components do not exist or function in isolation. To understand their biological importance, in addition to exploring individual components in more detail, we must integrate them into comprehensive models of cells, tissues, organs and organisms. This integration has been incomplete for somitogenesis, an early developmental process that establishes the first signs of segmentation in all vertebrates, patterning the precursors of the vertebrae, ribs, and skeletal muscles of the back and limbs. In this paper, we make significant progress towards a comprehensive model of somitogenesis by combining specialized hypotheses for specific subcomponent mechanisms of somitogenesis into a unified multi-scale model that successfully reproduces many characteristic events seen in the embryo.

Date: 2011
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1002155

DOI: 10.1371/journal.pcbi.1002155

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