Notch signaling controls proliferation through cell-autonomous and non-autonomous mechanisms in the Drosophila eye.
During Drosophila eye development, localized Notch signaling at the dorsal ventral (DV)-midline promotes growth of the entire eye field. This long-range action of Notch signaling may be mediated through the diffusible ligand of the Jak/STAT pathway, Unpaired (Upd), which was recently identified as a downstream target of Notch. However, Notch activity has not been shown to be cell-autonomously required for Upd expression and therefore yet another diffusible signal may be required for Notch activation of Upd. Our results clarify the Notch requirement, demonstrating that Notch activity at the DV-midline leads to cell-autonomous expression of Upd as monitored in loss and gain-of-function Notch clones. In addition, mutations in the Jak/STAT pathway interact genetically with the Notch pathway by suppressing Notch mediated overgrowth. N(act) clones show non-autonomous effects on the cell cycle anterior to the furrow, indicating function of the Jak/STAT pathway. However, cell-autonomous effects of Notch within and posterior to the furrow are independent of Upd. Here, Notch autonomously maintains cells in a proliferative state and blocks photoreceptor differentiation.
Reynolds-Kenneally
Jessica
J
Brookdale Department of Molecular, Cell and Developmental Biology, Mt. Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Mlodzik
Marek
M
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D019521:Body Patterning; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D005123:Eye / Q000166:cytology / Q000254:growth & development*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D017344:Genes, Insect; D053612:Janus Kinases; D008297:Male; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000254:growth & development; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology*; D050791:STAT Transcription Factors / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D029721:Drosophila Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D050791:STAT Transcription Factors; C105675:Stat92E protein, Drosophila; D014157:Transcription Factors; C115570:upd1 protein, Drosophila; D004247:DNA; D011505:Protein-Tyrosine Kinases; D053612:Janus Kinases; C085845:hop protein, Drosophila