@article{8a321aad0eb3408a82c8b24e06ca5072,
title = "Regulation of Numb during planar cell polarity establishment in the Drosophila eye",
abstract = "The establishment of planar cell polarity (PCP) in the Drosophila eye requires correct specification of the R3/R4 pair of photoreceptor cells, determined by a Frizzled mediated signaling event that specifies R3 and induces Delta to activate Notch signaling in the neighboring cell, specifying it as R4. Here, we investigated the role of the Notch signaling negative regulator Numb in the specification of R3/R4 fates and PCP establishment in the Drosophila eye. We observed that Numb is transiently upregulated in R3 at the time of R3/R4 specification. This regulation of Numb levels in developing photoreceptors occurs at the post-transcriptional level and is dependent on Dishevelled, an effector of Frizzled signaling, and Lethal Giant Larva. We detected PCP defects in cells homozygous for numb15, but these defects were due to a loss of function mutation in fat (fatQ805⁎) being present in the numb15 chromosome. However, mosaic overexpression of Numb in R4 precursors (only) caused PCP defects and numb loss-of-function alleles had a modifying effect on the defects found in a hypomorphic dishevelled mutation. Our results suggest that Numb levels are upregulated to reinforce the bias of Notch signaling activation in the R3/R4 pair, two post-mitotic cells that are not specified by asymmetric cell division.",
keywords = "Drosophila eye development, Fat, Numb, Planar cell polarity",
author = "Domingos, {Pedro M.} and Andreas Jenny and Combie, {Keon F.} and {del Alamo}, David and Marek Mlodzik and Hermann Steller and Bertrand Mollereau",
note = "Funding Information: We thank Seth Blair, Bingwei Lu, Sarah Bray, the Bloomington Drosophila Stock Center at the University of Indiana and the Developmental Studies Hybridoma Bank at the University of Iowa for fly strains and antibodies. We are grateful to Jurgen Knoblich for the numb 15 allele and discussions about our results. We thank Fran{\c c}ois Schweisguth for helpful discussions. H.S. was an Investigator with the Howard Hughes Medical Institute. This work was supported by the Strang Foundation and NIH grants from the National Eye Institute ( R01 EY14025 ) to BM and ( RO1 EY13256 ) to MM. Additional funding was granted to PMD ( FCT LISBOA-01-0145-FEDER-007660 , PTDC/NEU-NMC/2459/2014 and IF/00697/2014 , Portugal) and to BM ( ANR 13-ISV4-0003-01 ). Funding Information: We thank Seth Blair, Bingwei Lu, Sarah Bray, the Bloomington Drosophila Stock Center at the University of Indiana and the Developmental Studies Hybridoma Bank at the University of Iowa for fly strains and antibodies. We are grateful to Jurgen Knoblich for the numb15 allele and discussions about our results. We thank Fran?ois Schweisguth for helpful discussions. H.S. was an Investigator with the Howard Hughes Medical Institute. This work was supported by the Strang Foundation and NIH grants from the National Eye Institute (R01 EY14025) to BM and (RO1 EY13256) to MM. Additional funding was granted to PMD (FCT LISBOA-01-0145-FEDER-007660, PTDC/NEU-NMC/2459/2014 and IF/00697/2014, Portugal) and to BM (ANR 13-ISV4-0003-01). Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",
year = "2019",
month = dec,
doi = "10.1016/j.mod.2019.103583",
language = "English (US)",
volume = "160",
journal = "Mechanisms of Development",
issn = "0925-4773",
publisher = "Elsevier Ireland Ltd",
}