title: Boundary formation by notch signaling in Drosophila multicellular systems: experimental observations and gene network modeling by Genomic Object Net.
abstract: The Delta-Notch signaling system plays an essential role in various morphogenetic systems of multicellular animal development. Here we analyzed the mechanism of Notch-dependent boundary formation in the Drosophila large intestine, by experimental manipulation of Delta expression and computational modeling and simulation by Genomic Object Net. Boundary formation representing the situation in normal large intestine was shown by the simulation. By manipulating Delta expression in the large intestine, a few types of disorder in boundary cell differentiation were observed, and similar abnormal patterns were generated by the simulation. Simulation results suggest that parameter values representing the strength of cell-autonomous suppression of Notch signaling by Delta are essential for generating two different modes of patterning: lateral inhibition and boundary formation, which could explain how a common gene regulatory network results in two different patterning modes in vivo. Genomic Object Net proved to be a useful and flexible biosimulation system that is suitable for analyzing complex biological phenomena such as patternings of multicellular systems as well as intracellular changes in cell states including metabolic activities, gene regulation, and enzyme reactions.
authors.affiliation: Faculty of Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuno
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Murakami
authors.forename: Rie
authors.initials: R
authors.lastname: Yamane
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamasaki
authors.forename: Sachie
authors.initials: S
authors.lastname: Fujita
authors.forename: Haruka
authors.initials: H
authors.lastname: Yoshimori
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D019295:Computational Biology; D004330:Drosophila / Q000166:cytology / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D017344:Genes, Insect; D007420:Intestine, Large / Q000166:cytology / Q000196:embryology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics*; D008957:Models, Genetic; D051880:Receptors, Notch; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C064045:delta protein