Gene network dynamics controlling keratinocyte migration

Mol Syst Biol. 2008:4:199. doi: 10.1038/msb.2008.36. Epub 2008 Jul 1.

Abstract

Translation of large-scale data into a coherent model that allows one to simulate, predict and control cellular behavior is far from being resolved. Assuming that long-term cellular behavior is reflected in the gene expression kinetics, we infer a dynamic gene regulatory network from time-series measurements of DNA microarray data of hepatocyte growth factor-induced migration of primary human keratinocytes. Transferring the obtained interactions to the level of signaling pathways, we predict in silico and verify in vitro the necessary and sufficient time-ordered events that control migration. We show that pulse-like activation of the proto-oncogene receptor Met triggers a responsive state, whereas time sequential activation of EGF-R is required to initiate and maintain migration. Context information for enhancing, delaying or stopping migration is provided by the activity of the protein kinase A signaling pathway. Our study reveals the complex orchestration of multiple pathways controlling cell migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / genetics*
  • ErbB Receptors / genetics
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks*
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / physiology
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-met / genetics
  • Signal Transduction / genetics

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Hepatocyte Growth Factor
  • ErbB Receptors
  • Proto-Oncogene Proteins c-met