Delta and Egfr expression are regulated by Importin-7/Moleskin in Drosophila wing development

Abstract

Drosophila DIM-7 (encoded by the moleskin gene, msk) is the orthologue of vertebrate Importin-7. Both Importin-7 and Msk/DIM-7 function as nuclear import cofactors, and have been implicated in the control of multiple signal transduction pathways, including the direct nuclear import of the activated (phosphorylated) form of MAP kinase. We performed two genetic deficiency screens to identify deficiencies that similarly modified Msk overexpression phenotypes in both eyes and wings. We identified 11 total deficiencies, one of which removes the Delta locus. In this report, we show that Delta loss-of-function alleles dominantly suppress Msk gain-of-function phenotypes in the developing wing. We find that Msk overexpression increases both Delta protein expression and Delta transcription, though Msk expression alone is not sufficient to activate Delta protein function. We also find that Msk overexpression increases Egfr protein levels, and that msk gene function is required for proper Egfr expression in both developing wings and eyes. These results indicate a novel function for Msk in Egfr expression. We discuss the implications of these data with respect to the integration of Egfr and Delta/Notch signaling, specifically through the control of MAP kinase subcellular localization.

The role of nuclear pore complex in tumor microenvironment and metastasis

“…Interestingly, various cell surface receptor tyrosine kinases (RTKs), including EGFR, ErbB-2 and FGFR1, translocate to the nucleus by importin-β-dependent mechanisms [80]. Moreover, the putative NLS of EGFR and ErbB-2 has been identified and importin-β has been shown to interact with it [83,84].…”

Vibrio parahaemolyticus VopA Is a Potent Inhibitor of Cell Migration and Apoptosis in the Intestinal Epithelium of Drosophila melanogaster

“…1C). A tissue that requires a functional ERK pathway for development is the wing, where inhibition of ERK pathway signaling results in disruption of wing vein formation (29,30). Consistently, VopA expression under c765-GAL4 or with engrailed-GAL4 (en-GAL4), which targets expression to the posterior compartment of the wing, resulted in the complete loss of wing vein formation from the posterior wing ( Fig.…”

“…We created transgenic Drosophila flies harboring either upstream activation sequence (UAS)-myc-vopA or the catalytically inactive UAS-myc-mvopA (C181A) mutant form. Because a functional ERK pathway is necessary for the normal development of the Drosophila wing, disruption of ERK pathway signaling results in markedly altered phenotypes (28)(29)(30). We first detected expression of the transgenes by crossing fly lines harboring UAS-myc-vopA and UASmyc-mvopA to the heat shock (hs)-GAL4 driver line, which expresses the Saccharomyces cerevisiae yeast transactivator GAL4 in all cells upon incubation of Drosophila at 30°C (Fig.…”

IPO7 Promotes Odontoblastic Differentiation of Mouse Dental Papilla Cells by Selectively Importing Odontogenic Transcription Factors

“…In Runx2/Osx double heterozygous embryos, Ipo7 was downregulated in calvaria with reduced mineralized bones which indicates its role in bone development [25]. Previous studies also found that Ipo7 is involved in different stages of NE (neural ectoderm) differentiation [10] and overexpression of Ipo7 in drosophila in uences eye and wing development [26].…”

“…The importin β family involves in the nucleocytoplasmic transport processes of various proteins. IPO7, as a member of importin β family, participates in developmental processes [20], among which it functions as importing proteins. In this research, we focused on IPO7 and examined its potential function in regulating odontoblast differentiation in mDPCs.…”