Gene network dynamics controlling keratinocyte migration.

Hauke Busch, David Camacho-Trullio, Zbigniew Rogon, Kai Breuhahn, Peter Angel, Roland Eils, Axel Szabowski

Index: Mol. Syst. Biol. 4 , 199, (2008)

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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.