title: A computational model for BMP movement in sea urchin embryos.
abstract: Bone morphogen proteins (BMPs) are distributed along a dorsal-ventral (DV) gradient in many developing embryos. The spatial distribution of this signaling ligand is critical for correct DV axis specification. In various species, BMP expression is spatially localized, and BMP gradient formation relies on BMP transport, which in turn requires interactions with the extracellular proteins Short gastrulation/Chordin (Chd) and Twisted gastrulation (Tsg). These binding interactions promote BMP movement and concomitantly inhibit BMP signaling. The protease Tolloid (Tld) cleaves Chd, which releases BMP from the complex and permits it to bind the BMP receptor and signal. In sea urchin embryos, BMP is produced in the ventral ectoderm, but signals in the dorsal ectoderm. The transport of BMP from the ventral ectoderm to the dorsal ectoderm in sea urchin embryos is not understood. Therefore, using information from a series of experiments, we adapt the mathematical model of Mizutani et al. (2005) and embed it as the reaction part of a one-dimensional reaction-diffusion model. We use it to study aspects of this transport process in sea urchin embryos. We demonstrate that the receptor-bound BMP concentration exhibits dorsally centered peaks of the same type as those observed experimentally when the ternary transport complex (Chd-Tsg-BMP) forms relatively quickly and BMP receptor binding is relatively slow. Similarly, dorsally centered peaks are created when the diffusivities of BMP, Chd, and Chd-Tsg are relatively low and that of Chd-Tsg-BMP is relatively high, and the model dynamics also suggest that Tld is a principal regulator of the system. At the end of this paper, we briefly compare the observed dynamics in the sea urchin model to a version that applies to the fly embryo, and we find that the same conditions can account for BMP transport in the two types of embryos only if Tld levels are reduced in sea urchin compared to fly.
authors.affiliation: Mathematical Sciences School, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: van Heijster
authors.affiliation: Department of Mathematics, Christopher Newport University, Newport News, VA, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Hardway
authors.affiliation: Department of Mathematics and Statistics, Center for BioDynamics, Boston University, Boston, MA, USA.
authors.forename: Tasso J
authors.initials: TJ
authors.lastname: Kaper
authors.affiliation: Department of Biology, Program in Bioinformatics, Center for BioDynamics, Boston University, Boston, MA, USA. Electronic address: cbradham@bu.edu.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Bradham
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D004058:Diffusion; D029721:Drosophila Proteins / Q000378:metabolism; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D012617:Sea Urchins / Q000196:embryology*; D015398:Signal Transduction / Q000502:physiology*; D055394:Tolloid-Like Metalloproteinases / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; C090223:TSG protein, Drosophila; C091428:sog protein, Drosophila; D055394:Tolloid-Like Metalloproteinases
keywords: BMP signaling; Dorsal-ventral pattern formation; Echinoderm development; Reaction–diffusion equations