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Dynamic Rewiring of the Retinal Determination Network Switches Its Function from Selector to Differentiation


Organ development is directed by selector gene networks. Eye development in the fruit fly Drosophila melanogaster is driven by the highly conserved selector gene network referred to as the “retinal determination gene network,” composed of approximately 20 factors, whose core comprises twin of eyeless (toy), eyeless (ey), sine oculis (so), dachshund (dac), and eyes absent (eya). These genes encode transcriptional regulators that are each necessary for normal eye development, and sufficient to direct ectopic eye development when misexpressed. While it is well documented that the downstream genes so, eya, and dac are necessary not only during early growth and determination stages but also during the differentiation phase of retinal development, it remains unknown how the retinal determination gene network terminates its functions in determination and begins to promote differentiation. Here, we identify a switch in the regulation of ey by the downstream retinal determination genes, which is essential for the transition from determination to differentiation. We found that central to the transition is a switch from positive regulation of ey transcription to negative regulation and that both types of regulation require so. Our results suggest a model in which the retinal determination gene network is rewired to end the growth and determination stage of eye development and trigger terminal differentiation. We conclude that changes in the regulatory relationships among members of the retinal determination gene network are a driving force for key transitions in retinal development.


Vyšlo v časopise: Dynamic Rewiring of the Retinal Determination Network Switches Its Function from Selector to Differentiation. PLoS Genet 9(8): e32767. doi:10.1371/journal.pgen.1003731
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003731

Souhrn

Organ development is directed by selector gene networks. Eye development in the fruit fly Drosophila melanogaster is driven by the highly conserved selector gene network referred to as the “retinal determination gene network,” composed of approximately 20 factors, whose core comprises twin of eyeless (toy), eyeless (ey), sine oculis (so), dachshund (dac), and eyes absent (eya). These genes encode transcriptional regulators that are each necessary for normal eye development, and sufficient to direct ectopic eye development when misexpressed. While it is well documented that the downstream genes so, eya, and dac are necessary not only during early growth and determination stages but also during the differentiation phase of retinal development, it remains unknown how the retinal determination gene network terminates its functions in determination and begins to promote differentiation. Here, we identify a switch in the regulation of ey by the downstream retinal determination genes, which is essential for the transition from determination to differentiation. We found that central to the transition is a switch from positive regulation of ey transcription to negative regulation and that both types of regulation require so. Our results suggest a model in which the retinal determination gene network is rewired to end the growth and determination stage of eye development and trigger terminal differentiation. We conclude that changes in the regulatory relationships among members of the retinal determination gene network are a driving force for key transitions in retinal development.


Zdroje

1. Gilbert SF (2003) Developmental Biology. Sunderland: Sinauer Associates, Inc. 838 p.

2. Bodentstein D (1950) The Postembryonic development of Drosophila melanogaster. In: Demerec M, editor. Biology of Drosophila. New York: John Wiley and Sons, Inc. pp. 275–367.

3. Ferris GF (1950) External Morphology of the Adult. In: Demerec M, editor. Biology of Drosophila. New York: John Wiley and Sons, Inc. . pp. 368–419.

4. Cohen SM (1993) Imaginal Disc Development. In: Bate M, Martinez-Arias A, editors. The Development of Drosophila melanogaster: Cold Spring Harbor Laboratory Press. pp. 747–841.

5. HeberleinU, WolffT, RubinGM (1993) The TGF beta homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina. Cell 75: 913–926.

6. MaC, ZhouY, BeachyPA, MosesK (1993) The segment polarity gene hedgehog is required for progression of the morphogenetic furrow in the developing Drosophila eye. Cell 75: 927–938.

7. WolffT, ReadyDF (1991) The beginning of pattern formation in the Drosophila compound eye: the morphogenetic furrow and the second mitotic wave. Development 113: 841–850.

8. MannRS, CarrollSB (2002) Molecular mechanisms of selector gene function and evolution. Curr Opin Genet Dev 12: 592–600.

9. BoniniNM, BuiQT, Gray-BoardGL, WarrickJM (1997) The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates. Development 124: 4819–4826.

10. BoniniNM, LeisersonWM, BenzerS (1993) The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. Cell 72: 379–395.

11. CheyetteBN, GreenPJ, MartinK, GarrenH, HartensteinV, et al. (1994) The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron 12: 977–996.

12. HalderG, CallaertsP, GehringWJ (1995) Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267: 1788–1792.

13. MardonG, SolomonNM, RubinGM (1994) dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila. Development 120: 3473–3486.

14. QuiringR, WalldorfU, KloterU, GehringWJ (1994) Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. Science 265: 785–789.

15. ShenW, MardonG (1997) Ectopic eye development in Drosophila induced by directed dachshund expression. Development 124: 45–52.

16. WeasnerB, SalzerC, KumarJP (2007) Sine oculis, a member of the SIX family of transcription factors, directs eye formation. Dev Biol 303: 756–771.

17. CzernyT, HalderG, KloterU, SouabniA, GehringWJ, et al. (1999) twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development. Mol Cell 3: 297–307.

18. HalderG, CallaertsP, FlisterS, WalldorfU, KloterU, et al. (1998) Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development. Development 125: 2181–2191.

19. PappuKS, OstrinEJ, MiddlebrooksBW, SiliBT, ChenR, et al. (2005) Dual regulation and redundant function of two eye-specific enhancers of the Drosophila retinal determination gene dachshund. Development 132: 2895–2905.

20. BuiQT, ZimmermanJE, LiuH, BoniniNM (2000) Molecular analysis of Drosophila eyes absent mutants reveals features of the conserved Eya domain. Genetics 155: 709–720.

21. NiimiT, SeimiyaM, KloterU, FlisterS, GehringWJ (1999) Direct regulatory interaction of the eyeless protein with an eye-specific enhancer in the sine oculis gene during eye induction in Drosophila. Development 126: 2253–2260.

22. PauliT, SeimiyaM, BlancoJ, GehringWJ (2005) Identification of functional sine oculis motifs in the autoregulatory element of its own gene, in the eyeless enhancer and in the signalling gene hedgehog. Development 132: 2771–2782.

23. OstrinEJ, LiY, HoffmanK, LiuJ, WangK, et al. (2006) Genome-wide identification of direct targets of the Drosophila retinal determination protein Eyeless. Genome Res 16: 466–476.

24. PunzoC, SeimiyaM, FlisterS, GehringWJ, PlazaS (2002) Differential interactions of eyeless and twin of eyeless with the sine oculis enhancer. Development 129: 625–634.

25. SalzerCL, KumarJP (2009) Position dependent responses to discontinuities in the retinal determination network. Dev Biol 326: 121–130.

26. FirthLC, BakerNE (2009) Retinal determination genes as targets and possible effectors of extracellular signals. Dev Biol 327: 366–375.

27. ZhangT, RanadeS, CaiCQ, ClouserC, PignoniF (2006) Direct control of neurogenesis by selector factors in the fly eye: regulation of atonal by Ey and So. Development 133: 4881–4889.

28. Tanaka-MatakatsuM, DuW (2008) Direct control of the proneural gene atonal by retinal determination factors during Drosophila eye development. Dev Biol 313: 787–801.

29. JarmanAP, GrellEH, AckermanL, JanLY, JanYN (1994) Atonal is the proneural gene for Drosophila photoreceptors. Nature 369: 398–400.

30. KenyonKL, RanadeSS, CurtissJ, MlodzikM, PignoniF (2003) Coordinating proliferation and tissue specification to promote regional identity in the Drosophila head. Dev Cell 5: 403–414.

31. LiY, BakerNE (2001) Proneural enhancement by Notch overcomes Suppressor-of-Hairless repressor function in the developing Drosophila eye. Curr Biol 11: 330–338.

32. BakerNE, YuSY (1997) Proneural function of neurogenic genes in the developing Drosophila eye. Curr Biol 7: 122–132.

33. PignoniF, ZipurskySL (1997) Induction of Drosophila eye development by decapentaplegic. Development 124: 271–278.

34. CrewJR, BatterhamP, PollockJA (1997) Developing compound eye in lozenge mutants of Drosophila: lozenge expression in the R7 equivalence group. Development Genes and Evolution 206: 481–493.

35. FreemanM (1996) Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell 87: 651–660.

36. PignoniF, HuB, ZavitzKH, XiaoJ, GarrityPA, et al. (1997) The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell 91: 881–891.

37. PeppleKL, AtkinsM, VenkenK, WellnitzK, HardingM, et al. (2008) Two-step selection of a single R8 photoreceptor: a bistable loop between senseless and rough locks in R8 fate. Development 135: 4071–4079.

38. HauckB, GehringWJ, WalldorfU (1999) Functional analysis of an eye specific enhancer of the eyeless gene in Drosophila. Proc Natl Acad Sci U S A 96: 564–569.

39. VenkenKJ, HeY, HoskinsRA, BellenHJ (2006) P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 314: 1747–1751.

40. EkasLA, BaegGH, FlahertyMS, Ayala-CamargoA, BachEA (2006) JAK/STAT signaling promotes regional specification by negatively regulating wingless expression in Drosophila. Development 133: 4721–4729.

41. BaroloS, CarverLA, PosakonyJW (2000) GFP and beta-galactosidase transformation vectors for promoter/enhancer analysis in Drosophila. Biotechniques 29: 726, 728, 730, 732.

42. BessaJ, GebeleinB, PichaudF, CasaresF, MannRS (2002) Combinatorial control of Drosophila eye development by eyeless, homothorax, and teashirt. Genes Dev 16: 2415–2427.

43. PanD, RubinGM (1998) Targeted expression of teashirt induces ectopic eyes in Drosophila. Proc Natl Acad Sci U S A 95: 15508–15512.

44. KenyonKL, LiDJ, ClouserC, TranS, PignoniF (2005) Fly SIX-type homeodomain proteins Sine oculis and Optix partner with different cofactors during eye development. Dev Dyn 234: 497–504.

45. SilverSJ, DaviesEL, DoyonL, RebayI (2003) Functional dissection of eyes absent reveals new modes of regulation within the retinal determination gene network. Mol Cell Biol 23: 5989–5999.

46. AndersonAM, WeasnerBM, WeasnerBP, KumarJP (2012) Dual transcriptional activities of SIX proteins define their roles in normal and ectopic eye development. Development 139: 991–1000.

47. JemcJ, RebayI (2007) Identification of transcriptional targets of the dual-function transcription factor/phosphatase eyes absent. Dev Biol 310: 416–429.

48. SuzukiT, SaigoK (2000) Transcriptional regulation of atonal required for Drosophila larval eye development by concerted action of eyes absent, sine oculis and hedgehog signaling independent of fused kinase and cubitus interruptus. Development 127: 1531–1540.

49. CurtissJ, MlodzikM (2000) Morphogenetic furrow initiation and progression during eye development in Drosophila: the roles of decapentaplegic, hedgehog and eyes absent. Development 127: 1325–1336.

50. PappuKS, ChenR, MiddlebrooksBW, WooC, HeberleinU, et al. (2003) Mechanism of hedgehog signaling during Drosophila eye development. Development 130: 3053–3062.

51. HazelettDJ, BourouisM, WalldorfU, TreismanJE (1998) decapentaplegic and wingless are regulated by eyes absent and eyegone and interact to direct the pattern of retinal differentiation in the eye disc. Development 125: 3741–3751.

52. DominguezM, HafenE (1997) Hedgehog directly controls initiation and propagation of retinal differentiation in the Drosophila eye. Genes Dev 11: 3254–3264.

53. FuW, BakerNE (2003) Deciphering synergistic and redundant roles of Hedgehog, Decapentaplegic and Delta that drive the wave of differentiation in Drosophila eye development. Development 130: 5229–5239.

54. GreenwoodS, StruhlG (1999) Progression of the morphogenetic furrow in the Drosophila eye: the roles of Hedgehog, Decapentaplegic and the Raf pathway. Development 126: 5795–5808.

55. ChenR, AmouiM, ZhangZ, MardonG (1997) Dachshund and eyes absent proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell 91: 893–903.

56. IkedaK, WatanabeY, OhtoH, KawakamiK (2002) Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Mol Cell Biol 22: 6759–6766.

57. LeeT, LuoL (2001) Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development. Trends Neurosci 24: 251–254.

58. ShengG, ThouvenotE, SchmuckerD, WilsonDS, DesplanC (1997) Direct regulation of rhodopsin 1 by Pax-6/eyeless in Drosophila: evidence for a conserved function in photoreceptors. Genes Dev 11: 1122–1131.

59. SalzerCL, KumarJP (2010) Identification of retinal transformation hot spots in developing Drosophila epithelia. PLoS One 5: e8510.

60. LiX, OghiKA, ZhangJ, KronesA, BushKT, et al. (2003) Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature 426: 247–254.

61. BakerNE, FirthLC (2011) Retinal determination genes function along with cell-cell signals to regulate Drosophila eye development: examples of multi-layered regulation by master regulators. Bioessays 33: 538–546.

62. BachEA, EkasLA, Ayala-CamargoA, FlahertyMS, LeeH, et al. (2007) GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. Gene Expr Patterns 7: 323–331.

63. XuT, RubinGM (1993) Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117: 1223–1237.

64. JusiakB, AbulimitiA, HaeltermanN, ChenR, MardonG (2012) MAPK target sites of eyes absent are not required for eye development or survival in Drosophila. PLoS One 7: e50776.

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