The Bric-à-Brac BTB/POZ transcription factors are necessary in niche cells for germline stem cells establishment and homeostasis through control of BMP/DPP signaling in the Drosophila melanogaster ovary
Autoři:
Laurine Miscopein Saler aff001; Virginie Hauser aff001; Mathieu Bartoletti aff001; Charlotte Mallart aff001; Marianne Malartre aff001; Laura Lebrun aff001; Anne-Marie Pret aff002; Laurent Théodore aff001; Fabienne Chalvet aff001; Sophie Netter aff002
Působiště autorů:
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France
aff001; Université Paris-Saclay, UVSQ, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France
aff002
Vyšlo v časopise:
The Bric-à-Brac BTB/POZ transcription factors are necessary in niche cells for germline stem cells establishment and homeostasis through control of BMP/DPP signaling in the Drosophila melanogaster ovary. PLoS Genet 16(11): e32767. doi:10.1371/journal.pgen.1009128
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009128
Souhrn
Many studies have focused on the mechanisms of stem cell maintenance via their interaction with a particular niche or microenvironment in adult tissues, but how formation of a functional niche is initiated, including how stem cells within a niche are established, is less well understood. Adult Drosophila melanogaster ovary Germline Stem Cell (GSC) niches are comprised of somatic cells forming a stack called a Terminal Filament (TF) and associated Cap and Escort Cells (CCs and ECs, respectively), which are in direct contact with GSCs. In the adult ovary, the transcription factor Engrailed is specifically expressed in niche cells where it directly controls expression of the decapentaplegic (dpp) gene encoding a member of the Bone Morphogenetic Protein (BMP) family of secreted signaling molecules, which are key factors for GSC maintenance. In larval ovaries, in response to BMP signaling from newly formed niches, adjacent primordial germ cells become GSCs. The bric-à-brac paralogs (bab1 and bab2) encode BTB/POZ domain-containing transcription factors that are expressed in developing niches of larval ovaries. We show here that their functions are necessary specifically within precursor cells for TF formation during these stages. We also identify a new function for Bab1 and Bab2 within developing niches for GSC establishment in the larval ovary and for robust GSC maintenance in the adult. Moreover, we show that the presence of Bab proteins in niche cells is necessary for activation of transgenes reporting dpp expression as of larval stages in otherwise correctly specified Cap Cells, independently of Engrailed and its paralog Invected (En/Inv). Moreover, strong reduction of engrailed/invected expression during larval stages does not impair TF formation and only partially reduces GSC numbers. In the adult ovary, Bab proteins are also required for dpp reporter expression in CCs. Finally, when bab2 was overexpressed at this stage in somatic cells outside of the niche, there were no detectable levels of ectopic En/Inv, but ectopic expression of a dpp transgene was found in these cells and BMP signaling activation was induced in adjacent germ cells, which produced GSC-like tumors. Together, these results indicate that Bab transcription factors are positive regulators of BMP signaling in niche cells for establishment and homeostasis of GSCs in the Drosophila ovary.
Klíčová slova:
BMP signaling – Cell differentiation – Germ cells – Larvae – Ovaries – RNA interference – Stem cell niche – Transcription factors
Zdroje
1. Plaks V, Kong N, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell. 2015;16: 225–238. doi: 10.1016/j.stem.2015.02.015 25748930
2. Prager BC, Xie Q, Bao S, Rich JN. Cancer Stem Cells: The Architects of the Tumor Ecosystem. Cell Stem Cell. 2019;24: 41–53. doi: 10.1016/j.stem.2018.12.009 30609398
3. Zhao Y, Dong Q, Li J, Zhang K, Qin J, Zhao J, et al. Targeting cancer stem cells and their niche: perspectives for future therapeutic targets and strategies. Semin Cancer Biol. 2018;53: 139–155. doi: 10.1016/j.semcancer.2018.08.002 30081228
4. Ermolaeva M, Neri F, Ori A, Rudolph KL. Cellular and epigenetic drivers of stem cell ageing. Nat Rev Mol Cell Biol. 2018;19: 594–610. doi: 10.1038/s41580-018-0020-3 29858605
5. Aguado BA, Bushnell GG, Rao SS, Jeruss JS, Shea LD. Engineering the pre-metastatic niche. Nat Biomed Eng. 2017;1. doi: 10.1038/s41551-017-0077 28989814
6. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438: 820–827. doi: 10.1038/nature04186 16341007
7. Greenspan LJ, de Cuevas M, Matunis E. Genetics of gonadal stem cell renewal. Annu Rev Cell Dev Biol. 2015;31: 291–315. doi: 10.1146/annurev-cellbio-100913-013344 26355592
8. Xie T, Spradling AC. decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary. Cell. 1998;94: 251–260. doi: 10.1016/s0092-8674(00)81424-5 9695953
9. Gilboa L. Organizing stem cell units in the Drosophila ovary. Curr Opin Genet Dev. 2015;32: 31–36. doi: 10.1016/j.gde.2015.01.005 25703842
10. Panchal T, Chen X, Alchits E, Oh Y, Poon J, Kouptsova J, et al. Specification and spatial arrangement of cells in the germline stem cell niche of the Drosophila ovary depend on the Maf transcription factor Traffic jam. PLoS Genet. 2017;13: e1006790. doi: 10.1371/journal.pgen.1006790 28542174
11. Wang X, Page-McCaw A. Wnt6 maintains anterior escort cells as an integral component of the germline stem cell niche. Dev Camb Engl. 2018;145. doi: 10.1242/dev.158527 29361569
12. Song X, Call GB, Kirilly D, Xie T. Notch signaling controls germline stem cell niche formation in the Drosophila ovary. Dev Camb Engl. 2007;134: 1071–1080. doi: 10.1242/dev.003392 17287246
13. Xie T, Spradling AC. A niche maintaining germ line stem cells in the Drosophila ovary. Science. 2000;290: 328–330. doi: 10.1126/science.290.5490.328 11030649
14. Song X, Zhu C-H, Doan C, Xie T. Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science. 2002;296: 1855–1857. doi: 10.1126/science.1069871 12052957
15. Liu M, Lim TM, Cai Y. The Drosophila female germline stem cell lineage acts to spatially restrict DPP function within the niche. Sci Signal. 2010;3: ra57. doi: 10.1126/scisignal.2000740 20664066
16. Liu Z, Zhong G, Chai PC, Luo L, Liu S, Yang Y, et al. Coordinated niche-associated signals promote germline homeostasis in the Drosophila ovary. J Cell Biol. 2015;211: 469–484. doi: 10.1083/jcb.201503033 26504174
17. Luo L, Siah CK, Cai Y. Engrailed acts with Nejire to control decapentaplegic expression in the Drosophila ovarian stem cell niche. Dev Camb Engl. 2017;144: 3224–3231. doi: 10.1242/dev.145474 28928281
18. Song X, Wong MD, Kawase E, Xi R, Ding BC, McCarthy JJ, et al. Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary. Dev Camb Engl. 2004;131: 1353–1364. doi: 10.1242/dev.01026 14973291
19. Wang L, Li Z, Cai Y. The JAK/STAT pathway positively regulates DPP signaling in the Drosophila germline stem cell niche. J Cell Biol. 2008;180: 721–728. doi: 10.1083/jcb.200711022 18283115
20. Chen D, McKearin D. Dpp signaling silences bam transcription directly to establish asymmetric divisions of germline stem cells. Curr Biol CB. 2003;13: 1786–1791. doi: 10.1016/j.cub.2003.09.033 14561403
21. López-Onieva L, Fernández-Miñán A, González-Reyes A. Jak/Stat signalling in niche support cells regulates dpp transcription to control germline stem cell maintenance in the Drosophila ovary. Dev Camb Engl. 2008;135: 533–540. doi: 10.1242/dev.016121 18171682
22. Lu T, Wang S, Gao Y, Mao Y, Yang Z, Liu L, et al. COP9-Hedgehog axis regulates the function of the germline stem cell progeny differentiation niche in the Drosophila ovary. Dev Camb Engl. 2015;142: 4242–4252. doi: 10.1242/dev.124768 26672093
23. Rojas-Ríos P, Guerrero I, González-Reyes A. Cytoneme-mediated delivery of hedgehog regulates the expression of bone morphogenetic proteins to maintain germline stem cells in Drosophila. PLoS Biol. 2012;10: e1001298. doi: 10.1371/journal.pbio.1001298 22509132
24. Eliazer S, Palacios V, Wang Z, Kollipara RK, Kittler R, Buszczak M. Lsd1 restricts the number of germline stem cells by regulating multiple targets in escort cells. PLoS Genet. 2014;10: e1004200. doi: 10.1371/journal.pgen.1004200 24625679
25. McKearin D, Ohlstein B. A role for the Drosophila bag-of-marbles protein in the differentiation of cystoblasts from germline stem cells. Dev Camb Engl. 1995;121: 2937–2947. 7555720
26. Godt D, Laski FA. Mechanisms of cell rearrangement and cell recruitment in Drosophila ovary morphogenesis and the requirement of bric à brac. Dev Camb Engl. 1995;121: 173–187. 7867498
27. Sahut-Barnola I, Godt D, Laski FA, Couderc JL. Drosophila ovary morphogenesis: analysis of terminal filament formation and identification of a gene required for this process. Dev Biol. 1995;170: 127–135. doi: 10.1006/dbio.1995.1201 7601303
28. Cohen ED, Mariol M-C, Wallace RMH, Weyers J, Kamberov YG, Pradel J, et al. DWnt4 regulates cell movement and focal adhesion kinase during Drosophila ovarian morphogenesis. Dev Cell. 2002;2: 437–448. doi: 10.1016/s1534-5807(02)00142-9 11970894
29. Bartoletti M, Rubin T, Chalvet F, Netter S, Dos Santos N, Poisot E, et al. Genetic basis for developmental homeostasis of germline stem cell niche number: a network of Tramtrack-Group nuclear BTB factors. PloS One. 2012;7: e49958. doi: 10.1371/journal.pone.0049958 23185495
30. Green DA, Sarikaya DP, Extavour CG. Counting in oogenesis. Cell Tissue Res. 2011;344: 207–212. doi: 10.1007/s00441-011-1150-5 21384182
31. Sarikaya DP, Belay AA, Ahuja A, Dorta A, Green DA, Extavour CG. The roles of cell size and cell number in determining ovariole number in Drosophila. Dev Biol. 2012;363: 279–289. doi: 10.1016/j.ydbio.2011.12.017 22200592
32. Zhu C-H, Xie T. Clonal expansion of ovarian germline stem cells during niche formation in Drosophila. Dev Camb Engl. 2003;130: 2579–2588. doi: 10.1242/dev.00499 12736203
33. Lai C-M, Lin K-Y, Kao S-H, Chen Y-N, Huang F, Hsu H-J. Hedgehog signaling establishes precursors for germline stem cell niches by regulating cell adhesion. J Cell Biol. 2017;216: 1439–1453. doi: 10.1083/jcb.201610063 28363970
34. Couderc J-L, Godt D, Zollman S, Chen J, Li M, Tiong S, et al. The bric à brac locus consists of two paralogous genes encoding BTB/POZ domain proteins and acts as a homeotic and morphogenetic regulator of imaginal development in Drosophila. Dev Camb Engl. 2002;129: 2419–2433.
35. Green DA, Extavour CG. Convergent evolution of a reproductive trait through distinct developmental mechanisms in Drosophila. Dev Biol. 2012;372: 120–130. doi: 10.1016/j.ydbio.2012.09.014 23022298
36. Bolívar J, Pearson J, López-Onieva L, González-Reyes A. Genetic dissection of a stem cell niche: the case of the Drosophila ovary. Dev Dyn Off Publ Am Assoc Anat. 2006;235: 2969–2979. doi: 10.1002/dvdy.20967 17013875
37. Gustavson E, Goldsborough AS, Ali Z, Kornberg TB. The Drosophila engrailed and invected genes: partners in regulation, expression and function. Genetics. 1996;142: 893–906. 8849895
38. Chaharbakhshi E, Jemc JC. Broad-complex, tramtrack, and bric-à-brac (BTB) proteins: Critical regulators of development. Genes N Y N 2000. 2016;54: 505–518. doi: 10.1002/dvg.22964 27521773
39. Lours C, Bardot O, Godt D, Laski FA, Couderc J-L. The Drosophila melanogaster BTB proteins bric à brac bind DNA through a composite DNA binding domain containing a pipsqueak and an AT-Hook motif. Nucleic Acids Res. 2003;31: 5389–5398. doi: 10.1093/nar/gkg724 12954775
40. Gancz D, Lengil T, Gilboa L. Coordinated regulation of niche and stem cell precursors by hormonal signaling. PLoS Biol. 2011;9: e1001202. doi: 10.1371/journal.pbio.1001202 22131903
41. Mendes CC, Mirth CK. Stage-Specific Plasticity in Ovary Size Is Regulated by Insulin/Insulin-Like Growth Factor and Ecdysone Signaling in Drosophila. Genetics. 2016;202: 703–719. doi: 10.1534/genetics.115.179960 26715667
42. Forbes AJ, Spradling AC, Ingham PW, Lin H. The role of segment polarity genes during early oogenesis in Drosophila. Dev Camb Engl. 1996;122: 3283–3294. 8898240
43. Hsu H-J, Drummond-Barbosa D. Insulin signals control the competence of the Drosophila female germline stem cell niche to respond to Notch ligands. Dev Biol. 2011;350: 290–300. doi: 10.1016/j.ydbio.2010.11.032 21145317
44. Yatsenko AS, Shcherbata HR. Stereotypical architecture of the stem cell niche is spatiotemporally established by miR-125-dependent coordination of Notch and steroid signaling. Dev Camb Engl. 2018;145. doi: 10.1242/dev.159178 29361571
45. Gilboa L, Lehmann R. Repression of primordial germ cell differentiation parallels germ line stem cell maintenance. Curr Biol CB. 2004;14: 981–986. doi: 10.1016/j.cub.2004.05.049 15182671
46. Kai T, Spradling A. Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries. Nature. 2004;428: 564–569. doi: 10.1038/nature02436 15024390
47. Sato T, Ogata J, Niki Y. BMP and Hh signaling affects primordial germ cell division in Drosophila. Zoolog Sci. 2010;27: 804–810. doi: 10.2108/zsj.27.804 20887178
48. Matsuoka S, Hiromi Y, Asaoka M. Egfr signaling controls the size of the stem cell precursor pool in the Drosophila ovary. Mech Dev. 2013;130: 241–253. doi: 10.1016/j.mod.2013.01.002 23376160
49. Tseng C-Y, Su Y-H, Yang S-M, Lin K-Y, Lai C-M, Rastegari E, et al. Smad-Independent BMP Signaling in Somatic Cells Limits the Size of the Germline Stem Cell Pool. Stem Cell Rep. 2018;11: 811–827. doi: 10.1016/j.stemcr.2018.07.008 30122445
50. Sarikaya DP, Extavour CG. The Hippo pathway regulates homeostatic growth of stem cell niche precursors in the Drosophila ovary. PLoS Genet. 2015;11: e1004962. doi: 10.1371/journal.pgen.1004962 25643260
51. Cabrera GR, Godt D, Fang P-Y, Couderc J-L, Laski FA. Expression pattern of Gal4 enhancer trap insertions into the bric à brac locus generated by P element replacement. Genes N Y N 2000. 2002;34: 62–65. doi: 10.1002/gene.10115 12324949
52. Godt D, Couderc JL, Cramton SE, Laski FA. Pattern formation in the limbs of Drosophila: bric à brac is expressed in both a gradient and a wave-like pattern and is required for specification and proper segmentation of the tarsus. Dev Camb Engl. 1993;119: 799–812.
53. Roeske MJ, Camino EM, Grover S, Rebeiz M, Williams TM. Cis-regulatory evolution integrated the Bric-à-brac transcription factors into a novel fruit fly gene regulatory network. eLife. 2018;7. doi: 10.7554/eLife.32273 29297463
54. Chen D, McKearin DM. A discrete transcriptional silencer in the bam gene determines asymmetric division of the Drosophila germline stem cell. Dev Camb Engl. 2003;130: 1159–1170. doi: 10.1242/dev.00325 12571107
55. Ward EJ, Shcherbata HR, Reynolds SH, Fischer KA, Hatfield SD, Ruohola-Baker H. Stem cells signal to the niche through the Notch pathway in the Drosophila ovary. Curr Biol CB. 2006;16: 2352–2358. doi: 10.1016/j.cub.2006.10.022 17070683
56. Li MA, Alls JD, Avancini RM, Koo K, Godt D. The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila. Nat Cell Biol. 2003;5: 994–1000. doi: 10.1038/ncb1058 14578908
57. de Celis JF, Tyler DM, de Celis J, Bray SJ. Notch signalling mediates segmentation of the Drosophila leg. Dev Camb Engl. 1998;125: 4617–4626. 9806911
58. Sarov M, Barz C, Jambor H, Hein MY, Schmied C, Suchold D, et al. A genome-wide resource for the analysis of protein localisation in Drosophila. eLife. 2016;5: e12068. doi: 10.7554/eLife.12068 26896675
59. Li X, Yang F, Chen H, Deng B, Li X, Xi R. Control of germline stem cell differentiation by Polycomb and Trithorax group genes in the niche microenvironment. Dev Camb Engl. 2016;143: 3449–3458. doi: 10.1242/dev.137638 27510973
60. Zhao R, Xuan Y, Li X, Xi R. Age-related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila. Aging Cell. 2008;7: 344–354. doi: 10.1111/j.1474-9726.2008.00379.x 18267001
61. Kopp A, Duncan I, Godt D, Carroll SB. Genetic control and evolution of sexually dimorphic characters in Drosophila. Nature. 2000;408: 553–559. doi: 10.1038/35046017 11117736
62. Williams TM, Selegue JE, Werner T, Gompel N, Kopp A, Carroll SB. The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila. Cell. 2008;134: 610–623. doi: 10.1016/j.cell.2008.06.052 18724934
63. Chalvet F, Bartoletti M, Théodore L. Ovary phenotype and expression of bab1 and bab2 paralogs in the ovary of two mutants of bab locus in Drosophila melanogaster. Drosoph Info Serv. 2011; 158–62.
64. Bardot O, Godt D, Laski FA, Couderc J-L. Expressing UAS-bab1 and UAS-bab2: a comparative study of gain-of-function effects and the potential to rescue the bric à brac mutant phenotype. Genes N Y N 2000. 2002;34: 66–70. doi: 10.1002/gene.10124 12324950
65. Kudron MM, Victorsen A, Gevirtzman L, Hillier LW, Fisher WW, Vafeados D, et al. The ModERN Resource: Genome-Wide Binding Profiles for Hundreds of Drosophila and Caenorhabditis elegans Transcription Factors. Genetics. 2018;208: 937–949. doi: 10.1534/genetics.117.300657 29284660
66. Allbee AW, Rincon-Limas DE, Biteau B. Lmx1a is required for the development of the ovarian stem cell niche in Drosophila. Dev Camb Engl. 2018;145. doi: 10.1242/dev.163394 29615466
67. Margolis J, Spradling A. Identification and behavior of epithelial stem cells in the Drosophila ovary. Dev Camb Engl. 1995;121: 3797–3807. 8582289
68. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9: 676–682. doi: 10.1038/nmeth.2019 22743772
Článek vyšel v časopise
PLOS Genetics
2020 Číslo 11
- Může hubnutí souviset s vyšším rizikem nádorových onemocnění?
- Raději si zajděte na oční! Jak souvisí citlivost zraku s rozvojem demence?
- Co způsobuje pooperační infekce? Na vině může být i naše vlastní mikrobiota
- Čeká nás průlom v diagnostice karcinomu pankreatu?
- Polibek, který mi „vzal nohy“ aneb vzácný výskyt EBV u 70leté ženy – kazuistika
Nejčtenější v tomto čísle
- Stability of SARS-CoV-2 phylogenies
- Formal commentary
- No association between SCN9A and monogenic human epilepsy disorders
- Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis