Abstract
Epithelial cell extrusion is crucial for proper development and tissue homeostasis. High-resolution 3D reconstruction and 4D imaging, combined with genetic analyis, have allowed us to reveal the highly-sterotyped morphogenetic events controlled by JAK/STAT signaling in a developmentally-programmed case of epithelial cell extrusion. Specialized somatic cells, Polar Cells (PCs), are produced in excess and then undergo apoptotic elimination from the follicular epithelium in the Drosophila ovary. We show that supernumerary PCs are first systematically enveloped by PC neighbors on all sides, first laterally, then apically in conjunction with highly-reinforced adherens junctions, and finally basally. The PC to be removed thus loses all contact with follicle cells, germline cells and the basement membrane in a process we have called cell ‘monosis’, for ‘isolation’ in Greek. PC monosis takes several hours, and always precedes, and is independent of, activation of apoptosis. JAK/STAT signaling is necessary within the surrounding follicular epithelium for PC monosis. Minutes after monosis is complete, PC apoptotic corpses are formed and extruded laterally within the epithelium, in contrast to the apical and basal extrusions described to date. These apoptotic corpses are engulfed and eliminated by surrounding follicle cells, which are thus acting as non-professional phagocytes. This study therefore shows the non cell-autonomous impact of an epithelium, via JAK/STAT signaling activation, on cell morphogenesis events leading to apoptotic extrusion. It is likely that the use of high-resolution 3D and 4D imaging, which allows for better spatio-temporal understanding of morphogenetic events, will reveal that cell monosis and lateral extrusion within an epithelium are pertinent for other cases of epithelial cell extrusion as well.
Highlights
Cell extrusion is a process by which single cells are removed from an epithelium
We have shown that JAK/STAT activity is required for this process both in Polar cells (PCs) and neighboring follicle cells (FCs) to trigger the canonical Hid-Diap1-caspase apoptotic pathway to eliminate supernumerary PCs.[19,20]
Our results show that JAK/STAT signaling in the follicular epithelium drives PC monosis non cell-autonomously, which constitutes a prerequisite for apoptotic extrusion
Summary
Cell extrusion is a process by which single cells are removed from an epithelium. It is crucial for tissue morphogenesis and homeostasis. A few studies conducted in various developmental models and in cell culture have described specific cell remodeling events occuring during epithelial cell extrusion. These studies indicate a diversity of extrusion modalities, including either live or apoptotic cell extrusion,[2,3,4] apical or basal extrusion,[5,6,7] and different types of cell-cell contact exchanges.[3] A role for acto-myosin contraction, which can take place in the cell to be extruded and/or in the surrounding epithelial cells, has been reported.[8,9,10]. Real-time imaging has been used in some of these studies, high 3D resolution and additional non-induced cell extrusion models are needed to fully comprehend the cell remodeling events occurring at the cellular and tissue levels. Our results show that JAK/STAT signaling in the follicular epithelium drives PC monosis non cell-autonomously, which constitutes a prerequisite for apoptotic extrusion
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