Autophagy can promote but is not required for epithelial cell extrusion in the amnioserosa of the Drosophila embryo

Cormier, Olga; Mohseni, Nilufar; Voytyuk, Iryna; Reed, Bruce H.

doi:10.4161/auto.8.2.18618

Cited by 23 publications

(28 citation statements)

References 34 publications

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“…Quantification of LC3 A/B fluorescent intensity showed that K-Ras V12 extruding cells had consistently higher numbers of puncta (~2300 mean fluorescent intensity per 20 cells), compared to their non-extruding neighboring cells (~800 mean fluorescent intensity per 20 cells). The LC3 A/B increase in extruding cells may be similar to that seen in extruding cells in Drosophila amniosera prior to extrusion [20]. Extruding K-Ras V12 may have higher levels of autophagy than either wild type extruding or unextruding K-Ras V12 cells due to the fact that both K-Ras V12 signaling and extrusion signaling promote autophagy (as seen in Fig.…”

Section: Resultsmentioning

confidence: 76%

Autophagy in Oncogenic K-Ras Promotes Basal Extrusion of Epithelial Cells by Degrading S1P

Slattum

Sabbadini

et al. 2014

Current Biology

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Summary Background To maintain a protective barrier, epithelia extrude cells destined to die by contracting a band of actin and myosin. Although extrusion can remove cells triggered to die by apoptotic stimuli, to maintain constant cell numbers, epithelia extrude live cells, which later die by anoikis. Because transformed cells may override anoikis and survive after extrusion, the direction of extrusion has important consequences for the extruded cell’s fate. As most cells extrude apically, they are typically eliminated through the lumen, however, cells with upregulated survival signals that extrude basally could potentially invade the underlying tissue and migrate to other sites in the body. Results We found that oncogenic K-Ras cells predominantly extrude basally, rather than apically, in a cell-autonomous manner and can survive and proliferate following extrusion. Expressing K-RasV12 down-regulates the bioactive lipid Sphingosine 1-Phosphate (S1P) and its receptor S1P2, both of which are required for apical extrusion. Surprisingly, the S1P biosynthetic pathway is not affected, as the S1P precursor, sphingosine kinase, and the degradative enzymes S1P lyase and S1PP phosphatase are not significantly altered. Instead, we found that high levels of autophagy in extruding RasV12 cells leads to S1P degradation. Disruption of autophagy chemically or genetically in K-RasV12 cells rescues S1P localization and apical extrusion. Conclusions Oncogenic K-Ras cells down-regulate both S1P and its receptor S1P2 to promote basal extrusion. Because live basally extruding cells can survive and proliferate following extrusion, we propose that basal cell extrusion provides a novel mechanism for cells to exit the epithelium and initiate invasion into the surrounding tissues.

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Section: Resultsmentioning

confidence: 76%

Autophagy in Oncogenic K-Ras Promotes Basal Extrusion of Epithelial Cells by Degrading S1P

Slattum

Sabbadini

et al. 2014

Current Biology

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“…2D, F) suggesting an early onset of apoptosis. To visualize the effects of losses or gains of Egfr signaling on AS apoptosis in live embryos, we used the caspase sensor Apoliner [97], [98]. Apoliner consists of a monomeric red fluorescent protein (RFP) tethered to EGFP by a caspase-sensitive linker [97].…”

Section: Resultsmentioning

confidence: 99%

Modulation of Morphogenesis by Egfr during Dorsal Closure in Drosophila

et al. 2013

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During Drosophila embryogenesis the process of dorsal closure (DC) results in continuity of the embryonic epidermis, and DC is well recognized as a model system for the analysis of epithelial morphogenesis as well as wound healing. During DC the flanking lateral epidermal sheets stretch, align, and fuse along the dorsal midline, thereby sealing a hole in the epidermis occupied by an extra-embryonic tissue known as the amnioserosa (AS). Successful DC requires the regulation of cell shape change via actomyosin contractility in both the epidermis and the AS, and this involves bidirectional communication between these two tissues. We previously demonstrated that transcriptional regulation of myosin from the zipper (zip) locus in both the epidermis and the AS involves the expression of Ack family tyrosine kinases in the AS in conjunction with Dpp secreted from the epidermis. A major function of Ack in other species, however, involves the negative regulation of Egfr. We have, therefore, asked what role Egfr might play in the regulation of DC. Our studies demonstrate that Egfr is required to negatively regulate epidermal expression of dpp during DC. Interestingly, we also find that Egfr signaling in the AS is required to repress zip expression in both the AS and the epidermis, and this may be generally restrictive to the progression of morphogenesis in these tissues. Consistent with this theme of restricting morphogenesis, it has previously been shown that programmed cell death of the AS is essential for proper DC, and we show that Egfr signaling also functions to inhibit or delay AS programmed cell death. Finally, we present evidence that Ack regulates zip expression by promoting the endocytosis of Egfr in the AS. We propose that the general role of Egfr signaling during DC is that of a braking mechanism on the overall progression of DC.

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“…The amnioserosa is an extraembryonic tissue, and suffers histolysis in several forms: anoikis, autophagy, and apoptosis Toyama et al, 2008;Teng and Toyama, 2011;Cormier et al, 2012). For the lateral epidermis to completely surround the embryo, the two sets of lateral epidermal sheets must change shape and stretch over the amnioserosa toward the dorsal midline, and finally form a scarless continuum.…”

Section: Embryonic Dorsal Closurementioning

confidence: 99%

“…In this last, the mutant phenotype is more extreme, as the dorsal hole occupies the complete dorsal aspect of the cuticle, whereas the basket mutant cuticle showcases a hypomorphic condition, where some degree of closure (in the dorsal posterior aspect) is accrued. Subsequent quantitation of the phenomenon and, again, laser ablation studies showed that closure indeed would still happen in perturbed amnioserosal cell delamination and autophagy (Muliyil et al, 2011;Cormier et al, 2012). Data from in vivo microscopy analyses, laser ablation experiments and biophysical modeling led to the formulation of alternative hypotheses where amnioserosa cells, pulsing rythmically and periodically, generated also part of the force needed for closure (Solon et al, 2009;Blanchard et al, 2010).…”

Section: Embryonic Dorsal Closurementioning

confidence: 99%

Regulating cell morphogenesis: The drosophila jun N‐terminal kinase pathway

Ríos-Barrera

Riesgo-Escovar

2012

Genesis

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The Jun-N-terminal Kinase pathway (JNK), known also as stress activated protein kinase pathway (SAPK), is an eukaryotic evolutionarily conserved signaling pathway. From a purported evolutionarily "ancient" function as stress mediator, it evolved in multicellular eukaryotes to permanent roles in development, without leaving its original function. In Drosophila melanogaster, it is required for follicle cell morphogenesis, embryonic dorsal closure, pupal thoracic closure and genital disc rotation closure, all processes with requisite cell shape changes. Besides, it is activated during wound healing and in response to stress (UV irradiation, oxidative stress) where it may signal cell death or proliferation. Despite these varied roles, it has a conserved core of molecules that follow the MAPKKK/MAPKK/MAPK logic of mitogen activated protein kinases pathways. Regulation of the JNK pathway appears majorly negative, with phosphatases, transcription factors and proteins of novel structure "holding back" on JNK activation in different tissues. This particular mode of regulation may hark back to the pathway's origin as stress detector and responder, implying readiness to respond, from which the developmental roles may have evolved as conditions demanding obligate and predicted stress responses (i.e., embryonic dorsal closure viewed as a "wound of development").

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Autophagy can promote but is not required for epithelial cell extrusion in the amnioserosa of the Drosophila embryo

Cited by 23 publications

References 34 publications

Autophagy in Oncogenic K-Ras Promotes Basal Extrusion of Epithelial Cells by Degrading S1P

Autophagy in Oncogenic K-Ras Promotes Basal Extrusion of Epithelial Cells by Degrading S1P

Modulation of Morphogenesis by Egfr during Dorsal Closure in Drosophila

Regulating cell morphogenesis: The drosophila jun N‐terminal kinase pathway

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