Frizzled/PCP-dependent asymmetric neuralized expression determines R3/R4 fates in the Drosophila eye.
Planar cell polarity (PCP) is a common feature in many epithelia, reflected in cellular organization within the plane of an epithelium. In the Drosophila eye, Frizzled (Fz)/PCP signaling induces cell-fate specification of the R3/R4 photoreceptors through regulation of Notch activation in R4. Except for Dl upregulation in R3, the mechanism of how Fz/PCP signaling regulates Notch in this context is not understood. We demonstrate that the E3-ubiquitin ligase Neuralized (Neur), required for Dl-N signaling, is asymmetrically expressed within the R3/R4 pair. It is required in R3, where it is also upregulated in a Fz/PCP-dependent manner. As is the case for Dl, N activity in R4 further represses neur expression, thus, reinforcing the asymmetry. We demonstrate that Neur asymmetry is instructive in correct R3/R4 specification. Our data indicate that Fz/PCP-dependent Neur expression in R3 ensures the proper directionality of Dl-N signaling during R3/R4 specification.
del Alamo
David
D
Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Mlodzik
Marek
M
D000818:Animals; D030801:Animals, Genetically Modified; D019070:Cell Lineage; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D005123:Eye / Q000196:embryology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D017478:Receptors, Phencyclidine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D051157:Frizzled Receptors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D017478:Receptors, Phencyclidine; C064045:delta protein; C058784:fz protein, Drosophila; D044767:Ubiquitin-Protein Ligases; C071006:neur protein, Drosophila