title: A multi-cell, multi-scale model of vertebrate segmentation and somite formation.
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.
authors: Biocomplexity Institute and Department of Physics, Indiana University Bloomington, Bloomington, Indiana, United States of America. sdhester@umail.iu.edu
authors: Susan D
authors: SD
authors: Hester
authors: Julio M
authors: JM
authors: Belmonte
authors: J Scott
authors: JS
authors: Gens
authors: Sherry G
authors: SG
authors: Clendenon
authors: James A
authors: JA
authors: Glazier
mesh_terms: D000818:Animals; D001683:Biological Clocks; D019521:Body Patterning; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D002465:Cell Movement; D019295:Computational Biology; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D060509:Wnt3A Protein; C064045:delta protein; D051524:Fibroblast Growth Factor 8