Systems biology approach in unraveling the mechanism of cellular toxicity of auxinic herbicide

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The auxinic herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used to kill the weeds in crop fields. However, the molecular mechanism how it kills the dicot remains elusive. Previously, we provided evidence that 2,4-D degrades the cell cytoskeletal machinery and induces apoptosis through a novel auxin independent pathway (Rahman et al., 2007 ; Takahashi et al., manuscript in preparation). These results confirmed that the herbicidal action of 2,4-D is tightly linked to cellular toxicity instead of commonly believed acute auxin toxicity. To further clarify the mode of action of 2,4-D and unravel the molecular mechanism of its cellular toxicity, a systems biology approach was taken, which includes omics, bioinformatics and reverse genetics. Comparative transcriptome analysis between IAA and 2,4-D, identified distinct set of genes that are specifically responsive to 2,4-D. The Gene Ontology annotation analyses of these 2,4-D responsive genes reveal a group of genes that are linked to cell cytoskeletal component and apoptosis, confirming that 2,4-D kills the plant through actin degradation and subsequent apoptosis of cells. To understand the functional roles of the proteins that regulate this pathway, a reverse genetic approach has been taken.