Extracellular spreading of Wingless is required for Drosophila oogenesis
Autoři:
Xiaoxi Wang aff001; Kimberly S. LaFever aff001; Indrayani Waghmare aff001; Andrea Page-McCaw aff001
Působiště autorů:
Department of Cell and Developmental Biology, Program in Developmental Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
aff001
Vyšlo v časopise:
Extracellular spreading of Wingless is required for Drosophila oogenesis. PLoS Genet 17(4): e1009469. doi:10.1371/journal.pgen.1009469
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009469
Souhrn
Recent studies have investigated whether the Wnt family of extracellular ligands can signal at long range, spreading from their source and acting as morphogens, or whether they signal only in a juxtacrine manner to neighboring cells. The original evidence for long-range Wnt signaling arose from studies of Wg, a Drosophila Wnt protein, which patterns the wing disc over several cell diameters from a central source of Wg ligand. However, the requirement of long-range Wg for patterning was called into question when it was reported that replacing the secreted protein Wg with a membrane-tethered version, NRT-Wg, results in flies with normally patterned wings. We and others previously reported that Wg spreads in the ovary about 50 μm or 5 cell diameters, from the cap cells to the follicle stem cells (FSCs) and that Wg stimulates FSC proliferation. We used the NRT-wg flies to analyze the consequence of tethering Wg to the cap cells. NRT-wg homozygous flies are sickly, but we found that hemizygous NRT-wg/null flies, carrying only one copy of tethered Wingless, were significantly healthier. Despite their overall improved health, these hemizygous flies displayed dramatic reductions in fertility and in FSC proliferation. Further, FSC proliferation was nearly undetectable when the wg locus was converted to NRT-wg only in adults, and the resulting germarium phenotype was consistent with a previously reported wg loss-of-function phenotype. We conclude that Wg protein spreads from its source cells in the germarium to promote FSC proliferation.
Klíčová slova:
Toxicity – DAPI staining – Eggs – Homozygosity – Ovaries – Wnt signaling cascade – Juxtacrine signaling – Bird eggs
Zdroje
1. Steinhart Z, Angers S. Wnt signaling in development and tissue homeostasis. Development. 2018;145(11). doi: 10.1242/dev.146589 29884654.
2. Sharma RP, Chopra VL. Effect of the Wingless (wg1) mutation on wing and haltere development in Drosophila melanogaster. Dev Biol. 1976;48(2):461–5. doi: 10.1016/0012-1606(76)90108-1 815114.
3. Bejsovec A, Martinez Arias A. Roles of wingless in patterning the larval epidermis of Drosophila. Development. 1991;113(2):471–85. 1782860.
4. Kirkpatrick CA, Dimitroff BD, Rawson JM, Selleck SB. Spatial regulation of Wingless morphogen distribution and signaling by Dally-like protein. Dev Cell. 2004;7(4):513–23. doi: 10.1016/j.devcel.2004.08.004 15469840.
5. Kreuger J, Perez L, Giraldez AJ, Cohen SM. Opposing activities of Dally-like glypican at high and low levels of Wingless morphogen activity. Dev Cell. 2004;7(4):503–12. doi: 10.1016/j.devcel.2004.08.005 15469839.
6. Strigini M, Cohen SM. Wingless gradient formation in the Drosophila wing. Current Biology. 2000;10(6):293–300. doi: 10.1016/s0960-9822(00)00378-x WOS:000088977900014. 10744972
7. Struhl G, Basler K. Organizing activity of wingless protein in Drosophila. Cell. 1993;72(4):527–40. doi: 10.1016/0092-8674(93)90072-x 8440019.
8. Yan D, Lin X. Shaping morphogen gradients by proteoglycans. Cold Spring Harb Perspect Biol. 2009;1(3):a002493. Epub 2010/01/13. doi: 10.1101/cshperspect.a002493 20066107; PubMed Central PMCID: PMC2773635.
9. Zecca M, Basler K, Struhl G. Direct and long-range action of a wingless morphogen gradient. Cell. 1996;87(5):833–44. doi: 10.1016/s0092-8674(00)81991-1 8945511.
10. Alexandre C, Baena-Lopez A, Vincent JP. Patterning and growth control by membrane-tethered Wingless. Nature. 2014;505(7482):180–5. doi: 10.1038/nature12879 24390349.
11. Nusse R, Clevers H. Wnt/beta-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell. 2017;169(6):985–99. doi: 10.1016/j.cell.2017.05.016 28575679.
12. Beaven R, Denholm B. Release and spread of Wingless is required to pattern the proximo-distal axis of Drosophila renal tubules. Elife. 2018;7. doi: 10.7554/eLife.35373 30095068; PubMed Central PMCID: PMC6086663.
13. Tian A, Duwadi D, Benchabane H, Ahmed Y. Essential long-range action of Wingless/Wnt in adult intestinal compartmentalization. PLoS Genet. 2019;15(6):e1008111. doi: 10.1371/journal.pgen.1008111 31194729; PubMed Central PMCID: PMC6563961.
14. Chaudhary V, Hingole S, Frei J, Port F, Strutt D, Boutros M. Robust Wnt signaling is maintained by a Wg protein gradient and Fz2 receptor activity in the developing Drosophila wing. Development. 2019;146(15). doi: 10.1242/dev.174789 31399474; PubMed Central PMCID: PMC6703709.
15. Wang X, Page-McCaw A. A matrix metalloproteinase mediates long-distance attenuation of stem cell proliferation. J Cell Biol. 2014;206(7):923–36. doi: 10.1083/jcb.201403084 25267296; PubMed Central PMCID: PMC4178971.
16. Forbes AJ, Spradling AC, Ingham PW, Lin H. The role of segment polarity genes during early oogenesis in Drosophila. Development. 1996;122(10):3283–94. 8898240.
17. Song X, Xie T. Wingless signaling regulates the maintenance of ovarian somatic stem cells in Drosophila. Development. 2003;130(14):3259–68. doi: 10.1242/dev.00524 12783796.
18. Baeg GH, Lin X, Khare N, Baumgartner S, Perrimon N. Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless. Development. 2001;128(1):87–94. 11092814.
19. Han C, Yan D, Belenkaya TY, Lin X. Drosophila glypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc. Development. 2005;132(4):667–79. doi: 10.1242/dev.01636 15647319.
20. Luo L, Wang H, Fan C, Liu S, Cai Y. Wnt ligands regulate Tkv expression to constrain Dpp activity in the Drosophila ovarian stem cell niche. J Cell Biol. 2015;209(4):595–608. doi: 10.1083/jcb.201409142 26008746; PubMed Central PMCID: PMC4442805.
21. Kim-Yip RP, Nystul TG. Wingless promotes EGFR signaling in follicle stem cells to maintain self-renewal. Development. 2018;145(23). doi: 10.1242/dev.168716 30389852; PubMed Central PMCID: PMC6288384.
22. Sahai-Hernandez P, Nystul TG. A dynamic population of stromal cells contributes to the follicle stem cell niche in the Drosophila ovary. Development. 2013;140(22):4490–8. doi: 10.1242/dev.098558 24131631; PubMed Central PMCID: PMC3817939.
23. Waghmare I, Page-McCaw A. Wnt Signaling in Stem Cell Maintenance and Differentiation in the Drosophila Germarium. Genes (Basel). 2018;9(3). doi: 10.3390/genes9030127 29495453; PubMed Central PMCID: PMC5867848.
24. Wang S, Gao Y, Song X, Ma X, Zhu X, Mao Y, et al. Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche. Elife. 2015;4:e08174. doi: 10.7554/eLife.08174 26452202; PubMed Central PMCID: PMC4598714.
25. Melamed D, Kalderon D. Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders. Elife. 2020;9. doi: 10.7554/eLife.61204 33135631.
26. Kalderon D, Melamed D, Reilein A. Follicle Stem Cells (FSCs) in the Drosophila ovary; a critique of published studies defining the number, location and behavior of FSCs. bioRxiv. 2020:2020.06.25.171579. doi: 10.1101/2020.06.25.171579
27. Reilein A, Melamed D, Park KS, Berg A, Cimetta E, Tandon N, et al. Alternative direct stem cell derivatives defined by stem cell location and graded Wnt signalling. Nat Cell Biol. 2017;19(5):433–44. doi: 10.1038/ncb3505 28414313.
28. Fadiga J, Nystul TG. The follicle epithelium in the Drosophila ovary is maintained by a small number of stem cells. Elife. 2019;8. doi: 10.7554/eLife.49050 31850843; PubMed Central PMCID: PMC6946398.
29. Nystul T, Spradling A. Regulation of epithelial stem cell replacement and follicle formation in the Drosophila ovary. Genetics. 2010;184(2):503–15. doi: 10.1534/genetics.109.109538 19948890; PubMed Central PMCID: PMC2828728.
30. Laws KM, Drummond-Barbosa D. Genetic Mosaic Analysis of Stem Cell Lineages in the Drosophila Ovary. Methods Mol Biol. 2015;1328:57–72. doi: 10.1007/978-1-4939-2851-4_4 26324429; PubMed Central PMCID: PMC5512267.
31. Song X, Xie T. DE-cadherin-mediated cell adhesion is essential for maintaining somatic stem cells in the Drosophila ovary. Proceedings of the National Academy of Sciences of the United States of America. 2002;99(23):14813–8. Epub 2002/10/24. doi: 10.1073/pnas.232389399 12393817; PubMed Central PMCID: PMC137501.
32. Hartman TR, Strochlic TI, Ji Y, Zinshteyn D, O’Reilly AM. Diet controls Drosophila follicle stem cell proliferation via Hedgehog sequestration and release. J Cell Biol. 2013;201(5):741–57. doi: 10.1083/jcb.201212094 23690177; PubMed Central PMCID: PMC3664720.
33. Drummond-Barbosa D, Spradling AC. Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. Dev Biol. 2001;231(1):265–78. doi: 10.1006/dbio.2000.0135 11180967.
Článek vyšel v časopise
PLOS Genetics
2021 Číslo 4
- Proč jsou nemocnice nepřítelem spánku? A jak to změnit?
- Dlouhodobá ketodieta může poškozovat naše orgány
- „Jednohubky“ z klinického výzkumu – 2024/42
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Distribuce a lokalizace speciálně upravených exosomů může zefektivnit léčbu svalových dystrofií
Nejčtenější v tomto čísle
- Aicardi-Goutières syndrome-associated gene SAMHD1 preserves genome integrity by preventing R-loop formation at transcription–replication conflict regions
- Functional assessment of the “two-hit” model for neurodevelopmental defects in Drosophila and X. laevis
- Pathways and signatures of mutagenesis at targeted DNA nicks
- Using genetic variants to evaluate the causal effect of cholesterol lowering on head and neck cancer risk: A Mendelian randomization study