title: Computational insights into Caenorhabditis elegans vulval development.
abstract: Studies of Caenorhabditis elegans vulval development provide a paradigm for pattern formation during animal development. The fates of the six vulval precursor cells are specified by the combined action of an inductive signal that activates the EGF receptor mitogen-activated PK signaling pathway (specifying a primary fate) and a lateral signal mediated by LIN-12/Notch (specifying a secondary fate). Here we use methods devised for the engineering of complex reactive systems to model a biological system. We have chosen the visual formalism of statecharts and use it to formalize Sternberg and Horvitz's 1989 model [Sternberg, P. W. & Horvitz, H. R. (1989) Cell 58, 679-693], which forms the basis for our current understanding of the interaction between these two signaling pathways. The construction and execution of our model suggest that different levels of the inductive signal induce a temporally graded response of the EGF receptor mitogen-activated PK pathway and make explicit the importance of this temporal response. Our model also suggests the existence of an additional mechanism operating during lateral specification that prohibits neighboring vulval precursor cells from assuming the primary fate.
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. jasmine.fixher@weizmann.ac.il
authors.forename: Jasmin
authors.initials: J
authors.lastname: Fisher
authors.forename: Nir
authors.initials: N
authors.lastname: Piterman
authors.forename: E Jane Albert
authors.initials: EJ
authors.lastname: Hubbard
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stern
authors.forename: David
authors.initials: D
authors.lastname: Harel
mesh_terms: D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000033:anatomy & histology* / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage; D066246:ErbB Receptors / Q000378:metabolism; D008954:Models, Biological; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012984:Software; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors; C088818:lin-15A protein, C elegans; D011494:Protein Kinases; D066246:ErbB Receptors