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Deciphering signaling specificity in development, one phosphate at a time

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Receptor tyrosine kinases (RTKs) signal through shared intracellular pathways yet mediate distinct outcomes across many cell types. To investigate the mechanisms underlying RTK specificity, we have generated allelic series of mutations in PDGF and FGF receptor genes that prevent engagement of individual signaling pathways. These studies have provided insight into the mechanisms underlying signaling specificity, and identified both effector mediated outputs as well as responses originating from integration of multiple pathways. We have further identified distinct transcriptional programs, intracellular pathway usage, and cellular outcomes in response to these growth factors using RNA -Seq, in the context of craniofacial development. Collectively, our results delineate distinct responses to PDGF and FGF signaling in development. More generally, these studies provide insight into the mechanisms encoding transcriptional specificity in response to RTK signaling.

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