Cell elimination strategies upon identity switch via modulation of apterous in Drosophila wing disc


Autoři: Olga Klipa aff001;  Fisun Hamaratoglu aff001
Působiště autorů: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland aff001
Vyšlo v časopise: Cell elimination strategies upon identity switch via modulation of apterous in Drosophila wing disc. PLoS Genet 15(12): e32767. doi:10.1371/journal.pgen.1008573
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008573

Souhrn

The ability to establish spatial organization is an essential feature of any developing tissue and is achieved through well-defined rules of cell-cell communication. Maintenance of this organization requires elimination of cells with inappropriate positional identity, a poorly understood phenomenon. Here we studied mechanisms regulating cell elimination in the context of a growing tissue, the Drosophila wing disc and its dorsal determinant Apterous. Systematic analysis of apterous mutant clones along with their twin spots shows that they are eliminated from the dorsal compartment via three different mechanisms: relocation to the ventral compartment, basal extrusion, and death, depending on the position of the clone in the wing disc. We find that basal extrusion is the main elimination mechanism in the hinge, whereas apoptosis dominates in the pouch and in the notum. In the absence of apoptosis, extrusion takes over to ensure clearance in all regions. Notably, clones in the hinge grow larger than those in the pouch, emphasizing spatial differences. Mechanistically, we find that limiting cell division within the clones does not prevent their extrusion. Indeed, even clones of one or two cells can be extruded basally, demonstrating that the clone size is not the main determinant of the elimination mechanism to be used. Overall, we revealed three elimination mechanisms and their spatial biases for preserving pattern in a growing organ.

Klíčová slova:

Apoptosis – Cell cycle and cell division – Cell proliferation – Drosophila melanogaster – Epithelium – Notch signaling – Cellular extrusion


Zdroje

1. Morata G, Lawrence PA. Control of compartment development by the engrailed gene in Drosophila. Nature. 1975;255(5510):614–7. doi: 10.1038/255614a0 1134551

2. Kornberg T, Sidén I, O'Farrell P, Simon M. The engrailed locus of Drosophila: in situ localization of transcripts reveals compartment-specific expression. Cell. 1985;40(1):45–53. doi: 10.1016/0092-8674(85)90307-1 3917856

3. Diaz-Benjumea FJ, Cohen SM. Interaction between dorsal and ventral cells in the imaginal disc directs wing development in Drosophila. Cell. 1993;75(4):741–52. doi: 10.1016/0092-8674(93)90494-b 8242746

4. Couso JP, Knust E, Martinez Arias A. Serrate and wingless cooperate to induce vestigial gene expression and wing formation in Drosophila. Curr Biol. 1995;5(12):1437–48. doi: 10.1016/s0960-9822(95)00281-8 8749396

5. Klein T, Arias AM. Different spatial and temporal interactions between Notch, wingless, and vestigial specify proximal and distal pattern elements of the wing in Drosophila. Dev Biol. 1998;194(2):196–212. doi: 10.1006/dbio.1997.8829 9501029

6. Azpiazu N, Morata G. Function and regulation of homothorax in the wing imaginal disc of Drosophila. Development. 2000;127(12):2685–93. 10821766

7. Zirin JD, Mann RS. Differing strategies for the establishment and maintenance of teashirt and homothorax repression in the Drosophila wing. Development. 2004;131(22):5683–93. doi: 10.1242/dev.01450 15509768

8. Letizia A, Barrio R, Campuzano S. Antagonistic and cooperative actions of the EGFR and Dpp pathways on the iroquois genes regulate Drosophila mesothorax specification and patterning. Development. 2007;134(7):1337–46. doi: 10.1242/dev.02823 17329358

9. Bielmeier C, Alt S, Weichselberger V, La Fortezza M, Harz H, Jülicher F, et al. Interface Contractility between Differently Fated Cells Drives Cell Elimination and Cyst Formation. Curr Biol. 2016;26(5):563–74. doi: 10.1016/j.cub.2015.12.063 26853359

10. Giraldez AJ, Cohen SM. Wingless and Notch signaling provide cell survival cues and control cell proliferation during wing development. Development. 2003;130(26):6533–43. doi: 10.1242/dev.00904 14660542

11. Milán M, Pérez L, Cohen SM. Short-range cell interactions and cell survival in the Drosophila wing. Dev Cell. 2002;2(6):797–805. doi: 10.1016/s1534-5807(02)00169-7 12062091

12. Baena-Lopez LA, García-Bellido A. Control of growth and positional information by the graded vestigial expression pattern in the wing of Drosophila melanogaster. Proc Natl Acad Sci U S A. 2006;103(37):13734–9. doi: 10.1073/pnas.0606092103 16950871

13. Widmann TJ, Dahmann C. Wingless signaling and the control of cell shape in Drosophila wing imaginal discs. Dev Biol. 2009;334(1):161–73. doi: 10.1016/j.ydbio.2009.07.013 19627985

14. Villa-Cuesta E, González-Pérez E, Modolell J. Apposition of iroquois expressing and non-expressing cells leads to cell sorting and fold formation in the Drosophila imaginal wing disc. BMC Dev Biol. 2007;7:106. doi: 10.1186/1471-213X-7-106 17880703

15. Nellen D, Burke R, Struhl G, Basler K. Direct and long-range action of a DPP morphogen gradient. Cell. 1996;85(3):357–68. doi: 10.1016/s0092-8674(00)81114-9 8616891

16. Restrepo S, Zartman JJ, Basler K. Coordination of patterning and growth by the morphogen DPP. Curr Biol. 2014;24(6):R245–55. doi: 10.1016/j.cub.2014.01.055 24650915

17. Hamaratoglu F, Affolter M, Pyrowolakis G. Dpp/BMP signaling in flies: from molecules to biology. Semin Cell Dev Biol. 2014;32:128–36. doi: 10.1016/j.semcdb.2014.04.036 24813173

18. Baena-Lopez LA, Nojima H, Vincent JP. Integration of morphogen signalling within the growth regulatory network. Curr Opin Cell Biol. 2012;24(2):166–72. doi: 10.1016/j.ceb.2011.12.010 22257639

19. 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

20. Moreno E, Basler K, Morata G. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature. 2002;416(6882):755–9. doi: 10.1038/416755a 11961558

21. Adachi-Yamada T, O'Connor MB. Morphogenetic apoptosis: a mechanism for correcting discontinuities in morphogen gradients. Dev Biol. 2002;251(1):74–90. doi: 10.1006/dbio.2002.0821 12413899

22. Burke R, Basler K. Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing. Development. 1996;122(7):2261–9. 8681806

23. Johnston LA, Sanders AL. Wingless promotes cell survival but constrains growth during Drosophila wing development. Nat Cell Biol. 2003;5(9):827–33. doi: 10.1038/ncb1041 12942089

24. Gibson MC, Perrimon N. Extrusion and death of DPP/BMP-compromised epithelial cells in the developing Drosophila wing. Science. 2005;307(5716):1785–9. doi: 10.1126/science.1104751 15774762

25. Shen J, Dahmann C. Extrusion of cells with inappropriate Dpp signaling from Drosophila wing disc epithelia. Science. 2005;307(5716):1789–90. doi: 10.1126/science.1104784 15774763

26. Cohen B, McGuffin ME, Pfeifle C, Segal D, Cohen SM. apterous, a gene required for imaginal disc development in Drosophila encodes a member of the LIM family of developmental regulatory proteins. Genes Dev. 1992;6(5):715–29. doi: 10.1101/gad.6.5.715 1349545

27. Doherty D, Feger G, Younger-Shepherd S, Jan LY, Jan YN. Delta is a ventral to dorsal signal complementary to Serrate, another Notch ligand, in Drosophila wing formation. Genes Dev. 1996;10(4):421–34. doi: 10.1101/gad.10.4.421 8600026

28. Irvine KD, Wieschaus E. fringe, a Boundary-specific signaling molecule, mediates interactions between dorsal and ventral cells during Drosophila wing development. Cell. 1994;79(4):595–606. doi: 10.1016/0092-8674(94)90545-2 7954826

29. Panin VM, Papayannopoulos V, Wilson R, Irvine KD. Fringe modulates Notch-ligand interactions. Nature. 1997;387(6636):908–12. doi: 10.1038/43191 9202123

30. Diaz-Benjumea FJ, Cohen SM. Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. Development. 1995;121(12):4215–25. 8575321

31. Micchelli CA, Blair SS. Dorsoventral lineage restriction in wing imaginal discs requires Notch. Nature. 1999;401(6752):473–6. doi: 10.1038/46779 10519549

32. Blair SS, Brower DL, Thomas JB, Zavortink M. The role of apterous in the control of dorsoventral compartmentalization and PS integrin gene expression in the developing wing of Drosophila. Development. 1994;120(7):1805–15. 7924988

33. Bieli D, Kanca O, Requena D, Hamaratoglu F, Gohl D, Schedl P, et al. Establishment of a Developmental Compartment Requires Interactions between Three Synergistic Cis-regulatory Modules. PLoS Genet. 2015;11(10):e1005376. doi: 10.1371/journal.pgen.1005376 26468882

34. Bieli D, Kanca O, Gohl D, Denes A, Schedl P, Affolter M, et al. The Drosophila melanogaster Mutants apblot and apXasta Affect an Essential apterous Wing Enhancer. G3 (Bethesda). 2015;5(6):1129–43.

35. Lee LA, Orr-Weaver TL. Regulation of cell cycles in Drosophila development: intrinsic and extrinsic cues. Annu Rev Genet. 2003;37:545–78. doi: 10.1146/annurev.genet.37.110801.143149 14616073

36. Milán M, Cohen SM. A re-evaluation of the contributions of Apterous and Notch to the dorsoventral lineage restriction boundary in the Drosophila wing. Development. 2003;130(3):553–62. doi: 10.1242/dev.00276 12490561

37. Aliee M, Röper JC, Landsberg KP, Pentzold C, Widmann TJ, Jülicher F, et al. Physical mechanisms shaping the Drosophila dorsoventral compartment boundary. Curr Biol. 2012;22(11):967–76. doi: 10.1016/j.cub.2012.03.070 22560616

38. Michel M, Aliee M, Rudolf K, Bialas L, Jülicher F, Dahmann C. The Selector Gene apterous and Notch Are Required to Locally Increase Mechanical Cell Bond Tension at the Drosophila Dorsoventral Compartment Boundary. PLoS One. 2016;11(8):e0161668. doi: 10.1371/journal.pone.0161668 27552097

39. Vincent JP, Kolahgar G, Gagliardi M, Piddini E. Steep differences in wingless signaling trigger Myc-independent competitive cell interactions. Dev Cell. 2011;21(2):366–74. doi: 10.1016/j.devcel.2011.06.021 21839923

40. Legoff L, Rouault H, Lecuit T. A global pattern of mechanical stress polarizes cell divisions and cell shape in the growing Drosophila wing disc. Development. 2013;140(19):4051–9. doi: 10.1242/dev.090878 24046320

41. Tamori Y, Suzuki E, Deng WM. Epithelial Tumors Originate in Tumor Hotspots, a Tissue-Intrinsic Microenvironment. PLoS Biol. 2016;14(9):e1002537. doi: 10.1371/journal.pbio.1002537 27584724

42. Verghese S, Su TT. Drosophila Wnt and STAT Define Apoptosis-Resistant Epithelial Cells for Tissue Regeneration after Irradiation. PLoS Biol. 2016;14(9):e1002536. doi: 10.1371/journal.pbio.1002536 27584613

43. Baonza A, Garcia-Bellido A. Notch signaling directly controls cell proliferation in the Drosophila wing disc. Proc Natl Acad Sci U S A. 2000;97(6):2609–14. doi: 10.1073/pnas.040576497 10706613

44. Marinari E, Mehonic A, Curran S, Gale J, Duke T, Baum B. Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding. Nature. 2012;484(7395):542–5. doi: 10.1038/nature10984 22504180

45. Levayer R, Dupont C, Moreno E. Tissue Crowding Induces Caspase-Dependent Competition for Space. Curr Biol. 2016;26(5):670–7. doi: 10.1016/j.cub.2015.12.072 26898471

46. Hay BA, Wassarman DA, Rubin GM. Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. Cell. 1995;83(7):1253–62. doi: 10.1016/0092-8674(95)90150-7 8548811

Štítky
Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics


2019 Číslo 12

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se