Abstract
Wiring between signaling pathways differs according to context, as exemplified by interactions between Notch and epidermal growth factor receptor (EGFR) pathways, which are cooperative in some contexts but antagonistic in others. To investigate mechanisms that underlie different modes of cross talk, we have focused on argos, an EGFR pathway regulator in Drosophila melanogaster which is upregulated by Notch in adult muscle progenitors but is repressed in the wing. Results show that the alternate modes of cross talk depend on the engagement of enhancers with opposite regulatory logic, which are selected by context-determining factors. This is likely to be a general mechanism for enabling the wiring between these pathways to switch according to context.
Highlights
Wiring between signaling pathways differs according to context, as exemplified by interactions between Notch and epidermal growth factor receptor (EGFR) pathways, which are cooperative in some contexts but antagonistic in others
In adult muscle progenitors (AMPs), the epidermal growth factor receptor (EGFR) and Notch pathways appear to function cooperatively, and several EGFR pathway genes are directly upregulated in response to Notch activation [6]
As with other genes directly regulated by Notch, CSL is recruited to binding motifs in a known enhancer region of the argos gene, one of the EGFR pathway genes which is upregulated in the AMPs [6]
Summary
Wiring between signaling pathways differs according to context, as exemplified by interactions between Notch and epidermal growth factor receptor (EGFR) pathways, which are cooperative in some contexts but antagonistic in others. Results show that the alternate modes of cross talk depend on the engagement of enhancers with opposite regulatory logic, which are selected by contextdetermining factors This is likely to be a general mechanism for enabling the wiring between these pathways to switch according to context. In adult muscle progenitors (AMPs), the epidermal growth factor receptor (EGFR) and Notch pathways appear to function cooperatively, and several EGFR pathway genes are directly upregulated in response to Notch activation [6]. Binding of ligand (Delta or Serrate in Drosophila melanogaster) to the Notch receptor leads to the release of the Notch intracellular domain (Nicd) into the cytoplasm This fragment is able to interact directly with a transcription factor of the CSL family [Suppressor of Hairless; Su(H) in Drosophila]), leading to activation of target gene expression [16, 17]. These results demonstrate how opposite outputs can be generated by a signaling pathway through the context-specific engagement of enhancers with different regulatory logic
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