Ablation of germ-line precursor cells in Caenorhabditis elegansaging ͉ endocrine regulation ͉ reproduction ͉ longevity ͉ metabolism
The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. 59apically and are in contact with the intestinal lumen (Fig. 1A, Supplementary Fig. 1A). 60Therefore, we hypothesized that age-related changes in SJ could directly contribute to 74and an enriched analysis of the dataset revealed that the "cell adhesion" gene ontology 75(GO) category was one of the most representative GO categories that change with age 76(Supplementary Table1). The expression level of the majority of these genes (16 of 18) 77was up-regulated in old flies, indicating that decreased transcription is not a primary 78 mechanism contributing to age-related changes in SJs in the midgut. 79In Drosophila, SJ are divided into two classes based on morphological 95One striking and consistent age-related change in SJs was observed at tricellular 96 junctions (TCJ) (arrowheads, Fig. 1D-I, L-M, P-T), the specialized junction at the 101In the adult posterior midgut, Gli co-localized with Dlg ( Fig. 2A-B'; Supplementary 102 Fig. 2A-A''), as described previously in wing discs 16, 17 . Gli protein was clearly detected 103at EC-EC and EC-EE cell TCJ (Fig. 2 A,C,F); however, no Gli protein was detected in 104ISCs/EBs (Fig. 2D). In midguts from aged flies, Gli localization was largely absent from 105 the TCJ, and protein levels were increased in the cytoplasm (Fig. 2F-H). In hindguts, no 106 changes in Gli localization or protein levels were observed, similar to our observation for 107 other SJ proteins ( Supplementary Fig. 1P-Q). Interestingly, Dlg appeared cytoplasmic, 108rather than membrane-localized, in ISC/EB 'nests', suggesting that definitive SJ may be 109 absent between ISC/EBs and that formation of SJ is coordinated with differentiation. 110Consistent with this hypothesis, SJ were not apparent between ISCs and EBs via EM 111( Fig. 2E). 112Given the significant changes in TCJ (Fig. 1 D-M, P-T) and the striking loss of Gli 113from TCJ in older animals ( Fig. 2G-H age was a significant factor contributing to changes in TCJ (Fig. 2I, J) 118To determine whether compromised TCJ function could contribute to age-related 119 changes in the intestine, Gli was depleted from TCJs using a drug-inducible version of 120 the GAL4-UAS system 19, 20 . Targeted gene expression using the 5966 GS GAL4 "driver" 125Depletion of Gli from ECs resulted in an accelerated loss of barrier integrity (Fig. 1263A ; Supplementary Fig. 2E). Integrity of the intestinal barrier can be assayed by feeding 127 flies a non-absorbable blue food dye. When the intestinal barrier is intact, the dye is 128 retaine...
Adult stem cells reside in specialized microenvironments, or niches, that have an important role in regulating stem cell behaviour1. Therefore, tight control of niche number, size and function is necessary to ensure the proper balance between stem cells and progenitor cells available for tissue homeostasis and wound repair. The stem cell niche in the Drosophila male gonad is located at the tip of the testis where germline and somatic stem cells surround the apical hub, a cluster of approximately 10-15 somatic cells that is required for stem cell self-renewal and maintenance2-4. Here we show that somatic stem cells in the Drosophila testis contribute to both the apical hub and the somatic cyst cell lineage. The Drosophila orthologue of epithelial cadherin (DE-cadherin) is required for somatic stem cell maintenance and, consequently, the apical hub. Furthermore, our data indicate that the transcriptional repressor escargot regulates the ability of somatic cells to assume and/or maintain hub cell identity. These data highlight the dynamic relationship between stem cells and the niche and provide insight into genetic programmes that regulate niche size and function to support normal tissue homeostasis and organ regeneration throughout life.Many stem cell niches include support cells that influence stem cell behaviour through secretion of diffusible molecules. Physical contact between stem cells and support cells and/ or the extracellular matrix holds stem cells within the niche and close to self-renewal signals. Furthermore, niches provide spatial and mechanical cues that influence the fate of stem cell daughters. Therefore, the stem cell niche has an important role in regulating stem cell maintenance, self-renewal and survival (reviewed in ref. 5). However, little is known about the factors that regulate niche maintenance or size.Approximately ten somatic cells, called the hub, are found at the apical tip of the Drosophila testis (Fig. 1a)2. Germline stem cells (GSCs) and somatic stem cells (SSCs) surround and are in contact with hub cells. Whereas GSCs sustain spermatogenesis, SSCs produce cyst cells that encapsulate the maturing germ cells and ensure differentiation6,7. Hub cells secrete the growth factor Unpaired (Upd)3,4, which activates the JAK-STAT signal transduction pathway in adjacent stem cells. JAK-STAT signalling is necessary for stem cell maintenance and is sufficient to specify self-renewal of both GSCs and SSCs in the testis3,4,8.The apical hub is typically described as a post-mitotic, static structure. However, in agametic flies, SSCs proliferate and express hub markers, leading to an apparent expansion of the apical We proposed that SSCs may serve as a source of cells that contribute to the apical hub and, consequently, the stem cell niche. To address whether SSCs give rise to hub cells, positively marked β-galactosidase-expressing (β-gal + ) SSCs were generated using mitotic recombination, a technique typically used for lineage tracing analyses. Labelled SSCs were generated by heatshockin...
Adult stem cells support tissue homeostasis and repair throughout the life of an individual. During ageing, numerous intrinsic and extrinsic changes occur that result in altered stem-cell behaviour and reduced tissue maintenance and regeneration. In the Drosophila testis, ageing results in a marked decrease in the self-renewal factor Unpaired (Upd), leading to a concomitant loss of germline stem cells. Here we demonstrate that IGF-II messenger RNA binding protein (Imp) counteracts endogenous small interfering RNAs to stabilize upd (also known as os) RNA. However, similar to upd, Imp expression decreases in the hub cells of older males, which is due to the targeting of Imp by the heterochronic microRNA let-7. In the absence of Imp, upd mRNA therefore becomes unprotected and susceptible to degradation. Understanding the mechanistic basis for ageing-related changes in stem-cell behaviour will lead to the development of strategies to treat age-onset diseases and facilitate stem-cell-based therapies in older individuals.
Actin-based protrusions can form prominent structures on the apical surface of epithelial cells, such as microvilli. Several cytoplasmic factors have been identified that control the dynamics of actin filaments in microvilli. However, it remains unclear whether the plasma membrane participates actively in microvillus formation. In this paper, we analyze the function of Drosophila melanogaster cadherin Cad99C in the microvilli of ovarian follicle cells. Cad99C contributes to eggshell formation and female fertility and is expressed in follicle cells, which produce the eggshells. Cad99C specifically localizes to apical microvilli. Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length. Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain–binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length. This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.
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