A comparative study of Pointed and Yan expression reveals new complexity to the transcriptional networks downstream of receptor tyrosine kinase signaling.
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.
Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA; The Chicago Center for Systems Biology, The University of Chicago, Chicago, IL 60637, USA.
Jean-François
JF
Boisclair Lachance
Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA; The Chicago Center for Systems Biology, The University of Chicago, Chicago, IL 60637, USA.
Nicolás
N
Peláez
Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA; The Chicago Center for Systems Biology, The University of Chicago, Chicago, IL 60637, USA.
Justin J
JJ
Cassidy
Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA; The Chicago Center for Systems Biology, The University of Chicago, Chicago, IL 60637, USA.
Jemma L
JL
Webber
Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA; The Chicago Center for Systems Biology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: irebay@uchicago.edu.
Ilaria
I
Rebay
Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA; The Chicago Center for Systems Biology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: r-carthew@northwestern.edu.
Richard W
RW
Carthew
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000196:embryology; D005136:Eye Proteins / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
C076188:AOP protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C083884:pnt protein, Drosophila; D049452:Green Fluorescent Proteins; D020794:Receptor Protein-Tyrosine Kinases
Drosophila; EGFR signaling; ETS transcription factor; Embryo; Gene regulation; Imaginal discs