title: A model of the regulatory network involved in the control of the cell cycle and cell differentiation in the Caenorhabditis elegans vulva.
abstract: BACKGROUND
  There are recent experimental reports on the cross-regulation between molecules involved in the control of the cell cycle and the differentiation of the vulval precursor cells (VPCs) of Caenorhabditis elegans. Such discoveries provide novel clues on how the molecular mechanisms involved in the cell cycle and cell differentiation processes are coordinated during vulval development. Dynamic computational models are helpful to understand the integrated regulatory mechanisms affecting these cellular processes.
  
  
  RESULTS
  Here we propose a simplified model of the regulatory network that includes sufficient molecules involved in the control of both the cell cycle and cell differentiation in the C. elegans vulva to recover their dynamic behavior. We first infer both the topology and the update rules of the cell cycle module from an expected time series. Next, we use a symbolic algorithmic approach to find which interactions must be included in the regulatory network. Finally, we use a continuous-time version of the update rules for the cell cycle module to validate the cyclic behavior of the network, as well as to rule out the presence of potential artifacts due to the synchronous updating of the discrete model. We analyze the dynamical behavior of the model for the wild type and several mutants, finding that most of the results are consistent with published experimental results.
  
  
  CONCLUSIONS
  Our model shows that the regulation of Notch signaling by the cell cycle preserves the potential of the VPCs and the three vulval fates to differentiate and de-differentiate, allowing them to remain completely responsive to the concentration of LIN-3 and lateral signal in the extracellular microenvironment.
authors.affiliation: Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de, México, DF, México. nathan.weinstein@iibiomedicas.unam.mx.|Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, DF, México. nathan.weinstein@iibiomedicas.unam.mx.|Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, México, DF, México. nathan.weinstein@iibiomedicas.unam.mx.
authors.forename: Nathan
authors.initials: N
authors.lastname: Weinstein
authors.affiliation: Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de, México, DF, México. eortiz@lcg.unam.mx.|Instituto de Ecología, Universidad Nacional Autónoma de México, México, DF, México. eortiz@lcg.unam.mx.|Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, México, DF, México. eortiz@lcg.unam.mx.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ortiz-Gutiérrez
authors.affiliation: Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad, Nacional Autónoma de México, México, DF, México. stalinmunoz@yahoo.com.
authors.forename: Stalin
authors.initials: S
authors.lastname: Muñoz
authors.affiliation: Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad, Nacional Autónoma de México, México, DF, México. drosenbl@unam.mx.|Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, México, DF, México. drosenbl@unam.mx.
authors.forename: David A
authors.initials: DA
authors.lastname: Rosenblueth
authors.affiliation: Instituto de Ecología, Universidad Nacional Autónoma de México, México, DF, México. eabuylla@gmail.com.|Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, México, DF, México. eabuylla@gmail.com.
authors.forename: Elena R
authors.initials: ER
authors.lastname: Álvarez-Buylla
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, DF, México. lmendoza@biomedicas.unam.mx.|Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, México, DF, México. lmendoza@biomedicas.unam.mx.
authors.forename: Luis
authors.initials: L
authors.lastname: Mendoza
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division; D003198:Computer Simulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D008962:Models, Theoretical; D015398:Signal Transduction; D014844:Vulva / Q000166:cytology / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins