Determination of EGFR Signaling Output by Opposing Gradients of BMP and JAK/STAT Activity.
A relatively small number of signaling pathways drive a wide range of developmental decisions, but how this versatility in signaling outcome is generated is not clear. In the Drosophila follicular epithelium, localized epidermal growth factor receptor (EGFR) activation induces distinct cell fates depending on its location. Posterior follicle cells respond to EGFR activity by expressing the T-box transcription factors Midline and H15, while anterior cells respond by expressing the homeodomain transcription factor Mirror. We show that the choice between these alternative outputs of EGFR signaling is regulated by antiparallel gradients of JAK/STAT and BMP pathway activity and that mutual repression between Midline/H15 and Mirror generates a bistable switch that toggles between alternative EGFR signaling outcomes. JAK/STAT and BMP pathway input is integrated through their joint and opposing regulation of both sides of this switch. By converting this positional information into a binary decision between EGFR signaling outcomes, this regulatory network ultimately allows the same ligand-receptor pair to establish both the anterior-posterior (AP) and dorsal-ventral (DV) axes of the tissue.
Department of Biology, McGill University, 1205 Doctor Penfield Avenue, Montréal, QC H3A 1B1, Canada.
Mariana
M
Fregoso Lomas
Department of Biology, McGill University, 1205 Doctor Penfield Avenue, Montréal, QC H3A 1B1, Canada.
Scott
S
De Vito
Department of Biology, McGill University, 1205 Doctor Penfield Avenue, Montréal, QC H3A 1B1, Canada.
Jean-François
JF
Boisclair Lachance
Department of Biology, McGill University, 1205 Doctor Penfield Avenue, Montréal, QC H3A 1B1, Canada.
Josée
J
Houde
Department of Biology, McGill University, 1205 Doctor Penfield Avenue, Montréal, QC H3A 1B1, Canada. Electronic address: laura.nilson@mcgill.ca.
Laura A
LA
Nilson
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D018010:Receptors, Invertebrate Peptide / Q000235:genetics / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D029721:Drosophila Proteins; D018010:Receptors, Invertebrate Peptide; D050791:STAT Transcription Factors; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D053612:Janus Kinases