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JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade


Organogenesis is controlled by gene networks activated by upstream selector genes. To address how the network organization changes during development and how the target genes integrate the genetic information it provides, we analyze in Drosophila the induction of posterior spiracle organogenesis by the Hox gene Abdominal-B (Abd-B). Initially, Abd-B activates in the spiracle primordium a cascade of transcription factors and signalling molecules including the JAK/STAT pathway. We find that at later stages STAT activity feeds back into Abd-B, initiating the transformation of the Hox cascade into a gene-network. Focusing on a spiracle downstream target gene of Abd-B, we analyze how its cis regulatory elements integrate the dynamic network information set by Abd-B and the JAK/STAT signalling pathway during development. Our results also show that the well known transcription factor STAT can control gene expression as a “counter-repressor”, uncovering an alternative novel mode for STAT directed transcriptional regulation.


Vyšlo v časopise: JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005412
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005412

Souhrn

Organogenesis is controlled by gene networks activated by upstream selector genes. To address how the network organization changes during development and how the target genes integrate the genetic information it provides, we analyze in Drosophila the induction of posterior spiracle organogenesis by the Hox gene Abdominal-B (Abd-B). Initially, Abd-B activates in the spiracle primordium a cascade of transcription factors and signalling molecules including the JAK/STAT pathway. We find that at later stages STAT activity feeds back into Abd-B, initiating the transformation of the Hox cascade into a gene-network. Focusing on a spiracle downstream target gene of Abd-B, we analyze how its cis regulatory elements integrate the dynamic network information set by Abd-B and the JAK/STAT signalling pathway during development. Our results also show that the well known transcription factor STAT can control gene expression as a “counter-repressor”, uncovering an alternative novel mode for STAT directed transcriptional regulation.


Zdroje

1. Hombria JC, Lovegrove B (2003) Beyond homeosis—HOX function in morphogenesis and organogenesis. Differentiation 71: 461–476. 14641327

2. Hueber SD, Lohmann I (2008) Shaping segments: Hox gene function in the genomic age. Bioessays 30: 965–979. doi: 10.1002/bies.20823 18798525

3. Pearson JC, Lemons D, McGinnis W (2005) Modulating Hox gene functions during animal body patterning. Nat Rev Genet 6: 893–904. 16341070

4. Gehring WJ, Ikeo K (1999) Pax 6: mastering eye morphogenesis and eye evolution. Trends Genet 15: 371–377. 10461206

5. O'Hara E, Cohen B, Cohen SM, McGinnis W (1993) Distal-les is a downstream gene of Deformed required for ventral maxillary identity. Development 117: 847–856. 8100764

6. Sanchez-Higueras C, Sotillos S, Castelli-Gair Hombria J (2014) Common origin of insect trachea and endocrine organs from a segmentally repeated precursor. Curr Biol 24: 76–81. doi: 10.1016/j.cub.2013.11.010 24332544

7. Abrams EW, Vining MS, Andrew DJ (2003) Constructing an organ: the Drosophila salivary gland as a model for tube formation. Trends Cell Biol 13: 247–254. 12742168

8. Castelli Gair Hombria J, Rivas ML, Sotillos S (2009) Genetic control of morphogenesis—Hox induced organogenesis of the posterior spiracles. Int J Dev Biol 53: 1349–1358. doi: 10.1387/ijdb.072421jc 19247941

9. Desplan C (1997) Eye development: governed by a dictator or a junta? Cell 91: 861–864. 9428507

10. Sotillos S, Aguilar M, Hombria JC (2013) Forces shaping a Hox morphogenetic gene network. Proc Natl Acad Sci U S A 110: 4303–4308. doi: 10.1073/pnas.1212970110 23440219

11. Lovegrove B, Simoes S, Rivas ML, Sotillos S, Johnson K, et al. (2006) Coordinated control of cell adhesion, polarity, and cytoskeleton underlies Hox-induced organogenesis in Drosophila. Curr Biol 16: 2206–2216. 17113384

12. Tepass U (2012) The apical polarity protein network in Drosophila epithelial cells: regulation of polarity, junctions, morphogenesis, cell growth, and survival. Annu Rev Cell Dev Biol 28: 655–685. doi: 10.1146/annurev-cellbio-092910-154033 22881460

13. Tepass U, Theres C, Knust E (1990) crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell 61: 787–799. 2344615

14. Rivas ML, Cobreros L, Zeidler MP, Hombria JC (2008) Plasticity of Drosophila Stat DNA binding shows an evolutionary basis for Stat transcription factor preferences. EMBO Rep 9: 1114–1120. doi: 10.1038/embor.2008.170 18802449

15. Yan R, Small S, Desplan C, Dearolf CR, Darnell JE Jr. (1996) Identification of a Stat gene that functions in Drosophila development. Cell 84: 421–430. 8608596

16. Rivas ML, Espinosa-Vazquez JM, Sambrani N, Greig S, Merabet S, et al. (2013) Antagonism versus cooperativity with TALE cofactors at the base of the functional diversification of Hox protein function. PLoS Genet 9: e1003252. doi: 10.1371/journal.pgen.1003252 23408901

17. Jeong S, Rokas A, Carroll SB (2006) Regulation of body pigmentation by the Abdominal-B Hox protein and its gain and loss in Drosophila evolution. Cell 125: 1387–1399. 16814723

18. Williams TM, Selegue JE, Werner T, Gompel N, Kopp A, et al. (2008) The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila. Cell 134: 610–623. doi: 10.1016/j.cell.2008.06.052 18724934

19. Kvon EZ, Kazmar T, Stampfel G, Yanez-Cuna JO, Pagani M, et al. (2014) Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature 512: 91–95. doi: 10.1038/nature13395 24896182

20. Bradley PL, Haberman AS, Andrew DJ (2001) Organ formation in Drosophila: specification and morphogenesis of the salivary gland. Bioessays 23: 901–911. 11598957

21. Chung S, Chavez C, Andrew DJ (2011) Trachealess (Trh) regulates all tracheal genes during Drosophila embryogenesis. Dev Biol 360: 160–172. doi: 10.1016/j.ydbio.2011.09.014 21963537

22. Kerman BE, Cheshire AM, Andrew DJ (2006) From fate to function: the Drosophila trachea and salivary gland as models for tubulogenesis. Differentiation 74: 326–348. 16916373

23. Bonini NM, Bui QT, Gray-Board GL, Warrick JM (1997) The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates. Development 124: 4819–4826. 9428418

24. Chen R, Amoui M, Zhang Z, Mardon G (1997) Dachshund and eyes absent proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell 91: 893–903. 9428513

25. Pignoni F, Hu B, Zavitz KH, Xiao J, Garrity PA, 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. 9428512

26. Thuringer F, Bienz M (1993) Indirect autoregulation of a homeotic Drosophila gene mediated by extracellular signaling. Proc Natl Acad Sci U S A 90: 3899–3903. 8097881

27. García-Bellido A (1975) Genetic control of wing disc development in Drosophila. Amsterdam: Elsevier. 161–182 p.

28. Levy DE, Darnell JE Jr. (2002) Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 3: 651–662. 12209125

29. Hombria JC, Sotillos S (2013) JAK-STAT pathway in Drosophila morphogenesis: From organ selector to cell behavior regulator. JAKSTAT 2: e26089. doi: 10.4161/jkst.26089 24069568

30. Goenka S, Kaplan MH (2011) Transcriptional regulation by STAT6. Immunol Res 50: 87–96. doi: 10.1007/s12026-011-8205-2 21442426

31. Horvath CM (2000) STAT proteins and transcriptional responses to extracellular signals. Trends Biochem Sci 25: 496–502. 11050435

32. Ekas LA, Cardozo TJ, Flaherty MS, McMillan EA, Gonsalves FC, et al. (2010) Characterization of a dominant-active STAT that promotes tumorigenesis in Drosophila. Dev Biol 344: 621–636. doi: 10.1016/j.ydbio.2010.05.497 20501334

33. Shi S, Larson K, Guo D, Lim SJ, Dutta P, et al. (2008) Drosophila STAT is required for directly maintaining HP1 localization and heterochromatin stability. Nat Cell Biol 10: 489–496. doi: 10.1038/ncb1713 18344984

34. Li WX (2008) Canonical and non-canonical JAK-STAT signaling. Trends Cell Biol 18: 545–551. doi: 10.1016/j.tcb.2008.08.008 18848449

35. Shi S, Calhoun HC, Xia F, Li J, Le L, et al. (2006) JAK signaling globally counteracts heterochromatic gene silencing. Nat Genet 38: 1071–1076. 16892059

36. Hombria JC, Brown S, Hader S, Zeidler MP (2005) Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand. Dev Biol 288: 420–433. 16277982

37. Bach EA, Ekas LA, Ayala-Camargo A, Flaherty MS, Lee H, et al. (2007) GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. Gene Expr Patterns 7: 323–331. 17008134

38. Casanova J, Sanchez-Herrero E, Busturia A, Morata G (1987) Double and triple mutant combinations of bithorax complex of Drosophila. EMBO J 6: 3103–3109. 14650432

39. Makarova O, Kamberov E, Margolis B (2000) Generation of deletion and point mutations with one primer in a single cloning step. Biotechniques 29: 970–972. 11084856

40. Zhai Z, Yang X, Lohmann I (2011) Functional dissection of the Hox protein Abdominal-B in Drosophila cell culture. Biochem Biophys Res Commun 414: 761–766. doi: 10.1016/j.bbrc.2011.09.154 22005458

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