A comparative study of Pointed and Yan expression reveals new complexity to the transcriptional networks downstream of receptor tyrosine kinase signaling

• Published in: Developmental biology 2014-01, Vol.385 (2), p.263-278
• Main Authors: Boisclair Lachance, Jean-François, Peláez, Nicolás, Cassidy, Justin J., Webber, Jemma L., Rebay, Ilaria, Carthew, Richard W.
• Format: Article
• Language: English
• Subjects: Animals; DNA-Binding Proteins - genetics; Drosophila; Drosophila melanogaster - embryology; Drosophila Proteins - genetics; EGFR signaling; Embryo; ETS transcription factor; Eye Proteins - genetics; Gene regulation; gene regulatory networks; Green Fluorescent Proteins - genetics; Imaginal discs; loss-of-function mutation; Nerve Tissue Proteins - genetics; phenotype; protein synthesis; Proto-Oncogene Proteins - genetics; receptor protein-tyrosine kinase; Receptor Protein-Tyrosine Kinases - metabolism; repressor proteins; Repressor Proteins - genetics; Signal Transduction; tissues; transactivators; transcription (genetics); Transcription Factors - genetics; Transcription, Genetic; transgenes
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2013.11.002

The biochemical regulatory network downstream of receptor tyrosine kinase (RTK) signaling is controlled by two opposing ETS family members: the transcriptional activator Pointed (Pnt) and the transcriptional repressor Yan. A bistable switch model has been invoked to explain how pathway activation can drive differentiation by shifting the system from a high-Yan/low-Pnt activity state to a low-Yan/high-Pnt activity state. Although the model explains yan and pnt loss-of-function phenotypes in several different cell types, how Yan and Pointed protein expression dynamics contribute to these and other developmental transitions remains poorly understood. Toward this goal we have used a functional GFP-tagged Pnt transgene (Pnt-GFP) to perform a comparative study of Yan and Pnt protein expression throughout Drosophila development. Consistent with the prevailing model of the Pnt–Yan network, we found numerous instances where Pnt–GFP and Yan adopt a mutually exclusive pattern of expression. However we also observed many examples of co-expression. While some co-expression occurred in cells where RTK signaling is presumed low, other co-expression occurred in cells with high RTK signaling. The instances of co-expressed Yan and Pnt-GFP in tissues with high RTK signaling cannot be explained by the current model, and thus they provide important contexts for future investigation of how context-specific differences in RTK signaling, network topology, or responsiveness to other signaling inputs, affect the transcriptional response.