Highlights d The Drosophila posterior salivary gland imaginal ring is a transition-zone model d Persistent Notch signaling induces neoplastic transformation in the transition zone d Endogenous inflammatory JAK-STAT and JNK signaling promotes tumorigenesis d JNK-induced MMP1 shapes a weaker ECM structure for advanced tumorigenesis

The stem cell niche houses and regulates stem cells by providing both physical contact and local factors that regulate stem cell identity. The stem cell niche also plays a role in integrating niche-local and systemic signals, thereby ensuring that the balance of stem cells meets the needs of the organism. However, it is not clear how these signals are merged within the niche. Nutrient-sensing insulin/FOXO signaling has been previously shown to directly control Notch activation in the Drosophila female germline stem cell (GSC) niche, which maintains the niche and GSC identity. Here, we demonstrate that FOXO directly activates transcription of fringe, a gene encoding a glycosyltransferase that modulates Notch glycosylation. Fringe facilitates Notch inactivation in the GSC niche when insulin signaling is low. We also show that the Notch ligand predominantly involved is GSC niche-derived Delta. These results reveal that FOXO-mediated regulation of fringe links the insulin and Notch signaling pathways in the GSC niche in response to nutrition, and emphasize that stem cells are regulated by complex interactions between niche-local and systemic signals.

Immunocytochemistry was used to localize the populations of tyrosine-hydroxylase-like (TH)-immunoreactive cells in the tiger salamander retina. Ninety percent of these cells possessed somas that were situated in the innermost cell row of the inner nuclear layer and were classified as amacrine cells. Ten percent of TH-immunoreactive somas were located in the ganglion cell layer and were tentatively designated as those of displaced amacrine cells. The processes of TH-immunoreactive cells ramified most heavily in sublayer 1 of the inner plexiform layer, while a relatively small number of TH-labelled processes distributed in sublayers 3 and 5. Less than 1% of TH-immunoreactive cells in the amacrine cell layer exhibited a short process of somal origin that extended distally toward the outer plexiform layer. However, these processes did not cross the whole of the inner nuclear layer, and no immunolabelling was observed in the outer plexiform layer. An examination of retinal whole-mounts revealed that TH-immunoreactive amacrine and displaced amacrine cells were distributed throughout the center and periphery of the retina. The density of TH-immunolabelled amacrine cells was calculated to be 49 +/- 13 (mean +/- standard error) cells per mm2. The vast majority of TH-immunoreactive amacrine and displaced amacrine cells exhibited a stellate appearance and gave rise to three or more primary dendrites. A few TH-amacrine and displaced amacrine cells possessed two primary dendrites that emerged from opposite sides of their somas. The processes of TH-immunoreactive cells were generally poorly branched and varicose with terminal branches sometimes appearing thin and beaded. Because some TH-immunolabelled processes were very long, there was considerable overlap between the dendritic fields of neighboring TH-cells. Lastly, individual TH-immunoreactive amacrine and displaced amacrine cells were often observed in whole-mounts to provide processes that ramified at more than one level of the inner plexiform layer.

Highlights d Active Notch induces polyploid imaginal ring cells to re-enter mitosis d Polyploid mitosis, endoreplication, and depolyploidization together promote tumor growth d Ploidy-reduction division depends on genes involved in DNAdamage response and repair d Tumor progression correlates with increased ploidy heterogeneity and polyaneuploidy

Light microscopic immunocytochemistry was used to study the populations of serotoninlike-immunoreactive cells in the larval tiger salamander retina. Of 1,135 serotonin-immunostained cells observed in transverse cryosections, 87% were identified as amacrine cells, whereas 13% were tentatively designated as displaced amacrine cells. The somas of the vast majority of serotonin-amacrine cells were situated in the innermost cell row of the inner nuclear layer. Only a few serotonin-immunostained amacrine cell somas were observed in the second row of cells from the inner nuclear layer. Serotonin-immunoreactive processes generally appeared as a diffuse plexus distributed evenly throughout all levels of the inner plexiform layer. As determined in whole-mount preparations, serotonin-amacrine cells were divisible into two populations on the basis of the diameters of their somas. Large cells (45%) ranged from 16 to 19 microns in diameter with the vast majority measuring 17-18 microns. Smaller and sometimes less intensely stained cells ranged from 14 to 16 microns in diameter with the large majority measuring 15 microns. The diameters of serotonin-displaced amacrine cells ranged from 19 to 22 microns with the large majority measuring 20 microns in diameter. An examination of whole-mount retinas revealed that serotonin-immunoreactive amacrine and displaced amacrine cells were distributed throughout the center and the periphery of the retina. The density of serotonin-amacrine cells (large and small combined) was calculated to be 173 +/- 4.5 (mean +/- standard error) cells per mm2.