Gene expression dynamics reveal Sprouty mediated regulation of Wnt pathway genes

Sprouty genes (Spry) are feedback regulators of receptor tyrosine kinase signaling, and are genes with known tumor suppressing activity. The impact of Spry induction is ligand specific, but it is well-understood to be a negative feedback regulator of the mitogen-activated protein kinase pathway in response to fibroblast growth factor (FGF). However, the precise impact Spry has on transcription resulting in tumor suppression remains unknown. We use DiffExPy to analyze time-series gene expression data in Spry124fl/fl and Spry124-/- murine embryonic fibroblasts (MEFs). We show that the expression dynamics of Spry in response to FGF encode transcriptional regulation that spans RNA production, metabolism, and apoptotic processes. We also present results that suggest Spry regulates the angio- and oncogenic gene connective tissue growth factor (Ctgf ) via the Wnt signaling pathway. Our results clarify the transcriptional role of Spry, and provide quantitative, testable models of gene expression that can be applied and validated in different experimental contexts. We assessed gene expression changes upon loss of feedback regulation through Sprouty (Spry) deletion. Spry124fl/fl (WT) and Spry124-/- (KO) MEFs were profiled at 0, 15, 60, 120, and 240min after FGF treatment. Microarray profiling was performed in biological triplicate, except at 0min which, was conducted in quadruplicate. The genetic condition, replicate, and time point is included in the sample name.