EGF receptor signaling triggers recruitment of Drosophila sense organ precursors by stimulating proneural gene autoregulation.
In Drosophila, commitment of a cell to a sense organ precursor (SOP) fate requires bHLH proneural transcription factor upregulation, a process that depends in most cases on the interplay of proneural gene autoregulation and inhibitory Notch signaling. A subset of SOPs are selected by a recruitment pathway involving EGFR signaling to ectodermal cells expressing the proneural gene atonal. We show that EGFR signaling drives recruitment by directly facilitating atonal autoregulation. Pointed, the transcription factor that mediates EGFR signaling, and Atonal protein itself bind cooperatively to adjacent conserved binding sites in an atonal enhancer. Recruitment is therefore contingent on the combined presence of Atonal protein (providing competence) and EGFR signaling (triggering recruitment). Thus, autoregulation is the nodal control point targeted by signaling. This exemplifies a simple and general mechanism for regulating the transition from competence to cell fate commitment whereby a cell signal directly targets the autoregulation of a selector gene.
zur Lage
Petra I
PI
Division of Biomedical Sciences, Centre for Neuroscience Research, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
Powell
Lynn M
LM
Prentice
David R A
DR
McLaughlin
Paul
P
Jarman
Andrew P
AP
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D066246:ErbB Receptors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012679:Sense Organs / Q000196:embryology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D066246:ErbB Receptors; D005982:Glutathione Transferase; D049452:Green Fluorescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C497759:N protein, Drosophila; C082142:ato protein, Drosophila; C083884:pnt protein, Drosophila