The Spalt Transcription Factors Generate the Transcriptional Landscape of the Wing Pouch Central Region

English version České info

How signalling pathways regulate the formation of organs with a precise size and pattern of differentiation is a fundamental question in developmental genetics. One classical example of the link between signalling and organ development is the regulation of wing disc development by the Decapentaplegic/BMP (Dpp) signalling pathway in Drosophila. A key outcome of this pathway is the transcriptional activation of the spalt major (salm) and spalt related (salr) genes, both encoding transcription factors. In this manner, the identification of Salm/Salr target genes is a critical step towards the understanding of the mode of action of these proteins and the genetic logic underlying the regulation of wing development by the Dpp signalling pathway. In order to identify these target genes, we used expression microarrays, in situ hybridization and phenotypic analysis. We identified an unexpected complexity in the transcriptional landscape of the wing disc that includes genes positively and negatively regulated by Salm/Salr. These findings have major implications for the reconstruction of the genetic hierarchy initiated by the Dpp pathway and leading to the formation of a wing with a correct size and pattern, because some of the genes we identified could explain particular aspects of the sal mutant phenotype.

Vyšlo v časopise: The Spalt Transcription Factors Generate the Transcriptional Landscape of the Wing Pouch Central Region. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005370
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005370

Souhrn

Zdroje

1. Beira JV, Springhorn A, Gunther S, Hufnagel L, Pyrowolakis G, Vincent JP (2014) The Dpp/TGFbeta-Dependent Corepressor Schnurri Protects Epithelial Cells from JNK-Induced Apoptosis in Drosophila Embryos. Developmental Cell 31: 240–247. doi: 10.1016/j.devcel.2014.08.015 25307481

2. Affolter M, Basler K (2007) The Decapentaplegic morphogen gradient: from pattern formation to growth regulation. Nature Rew. Genetics, 8: 663–674. 17703237

3. de Celis J (2003) Pattern formation in the Drosophila wing: The development of the veins. BioEssays 25: 443–451. 12717815

4. Grimm S, Pflugfelder GO (1996) Control of the gene optomotor-blind in Drosophila wing development by decapentaplegic and wingless. Science 271:1601–1604.

5. de Celis JF, Barrio R, Kafatos FC (1996) A gene complex acting downstream of dpp in Drosophila wing morphogenesis. Nature 381: 421–424. 8632798

6. Umemori M, Takemura M, Maeda K, Ohba K, Adachi-Yamada T (2007) Drosophila T-box transcription factor Optomotor-blind prevents pathological folding and local overgrowth in wing epithelium through confining Hh signal. Dev Biol 308: 68–81. 17573067

7. Shen J, Dahmann C, Pflugfelder G (2010) Spatial discontinuity of Optomotor-blind expression in the Drosophila wing imaginal disc disrupts epithelial architecture and promotes cell sorting. BMC Dev Biol 10: 23.

8. Organista MF, De Celis JF (2013) The Spalt transcription factors regulate cell proliferation, survival and epithelial integrity downstream of the Decapentaplegic signalling pathway. Biology Open 2: 37–48.

9. de Celis JF, Barrio R (2009) Regulation and function of Spalt proteins during animal development. The International Journal of Developmental Biology 53: 1385–1398. doi: 10.1387/ijdb.072408jd 19247946

10. Kohlhase J, Wischermann A, Reichenbach H, Froster U, Engel W (1998) Mutations in the SALL1 putative transcription factor gene cause Townes- Brocks syndrome. Nat Genet 18: 81–83. 9425907

11. Kohlhase J, Heinrich M, Liebers M, Frohlich Archangelo L, Reardon W, Kispert A (2002) Cloning and expression analysis of SALL4, the murine homologue of the gene mutated in Okihiro syndrome. Cytogenetic and Genome Research 98: 274–277. 12826753

12. Al-Baradie R, Yamada K, St Hilaire C, Chan WM, Andrews C, McIntosh N, Nakano M, Martonyi EJ, Raymond WR, Okumura S, et al (2002) Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. American Journal of Human Genetics 71: 1195–1199. 12395297

13. Netzer C, Rieger L, Brero A, Zhang C, Hinzke M, et al. (2001) SALL1, the gene mutated in Townes-Brocks syndrome, encodes a transcriptional repressor which interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin. Hum Mol Genet 10: 3017–3024. 11751684

14. Netzer C, Bohlander S, Hinzke M, Chen Y, L K (2006) Defining the heterochromatin localization and repression domains of SALL1. Biochim Biophys Acta 1762: 386–391. 16443351

15. Sánchez J, Talamillo A, González M, Sánchez-Pulido L, Jiménez S, Pirone L, Sutherland J, Barrio R (2011) Drosophila Sal and Salr are transcriptional repressors. Biochem J 438: 437–445. doi: 10.1042/BJ20110229 21689070

16. Wu Q, Chen X, Zhang J, Loh Y, Low T, et al. (2006) Sall4 Interacts with Nanog and Co-occupies Nanog Genomic Sites in Embryonic Stem Cells. J Biol Chem 281: 24090–24094. 16840789

17. Yamashita K, Sato A, Asashima M, PC W, Nishinakamura R (2007) Mouse homolog of SALL1, a causative gene for Townes-Brocks syndrome, binds to A/T-rich sequences in pericentric heterochromatin via its Cterminal zinc finger domains. Genes Cells 12:171–182. 17295837

18. Zhang J, Tam W, Tong G, Wu Q, Chan H, et al (2006) Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol 8: 1114–1123. 16980957

19. Lunde K, Biehs B, Neuber U, Bier E (1998) The knirps and knirps-related genes organize development of the second wing vein in Drosphila. Development 125: 4145–4154. 9753669

20. de Celis J, Barrio R (2000) Function of the spalt/spalt-related gene complex in positioning the veins in the Drosophila wing. Mech Dev 91: 31–41. 10704828

21. Milan M, Perez L, Cohen SM (2002) Short-range cell interactions and cell survival in the Drosophila wing. Developmental Cell 2: 797–805. 12062091

22. Barrio R, de Celis JF (2004) Regulation of spalt expression in the Drosophila wing blade in response to the Decapentaplegic signalling pathway. PNAS 101: 6021–6026.

23. Cruz C, Glavic A, Casado M, de Celis JF (2009) A gain-of-function screen identifying genes required for growth and pattern formation of the Drosophila melanogaster wing. Genetics 183: 1005–1026. doi: 10.1534/genetics.109.107748 19737745

24. McGuire S, Le P, Osborn A, Matsumoto K, Davis R (2003) Spatiotemporal rescue of memory dysfunction in Drosophila. Science 302: 1765–1768. 14657498

25. Butler MJ, Jacobsen TL, Cain DM, Jarman MG, Hubank M, Whittle JS, Phillips R, Simcox A (2003) Discovery of genes with highly restricted expression patterns in the Drosophila wing disc using DNA oligonucleotide microarrays. Development 130: 659–670. 12505997

26. Doumpas N, Ruiz‐Romero M, Blanco E, Edgar B, Corominas M, Teleman AA (2013) Brk regulates wing disc growth in part via repression of Myc expression. EMBO reports 14, 261–268. doi: 10.1038/embor.2013.1 23337628

27. Ferreiro MJ, Rodríguez-Ezpeleta N, Pérez C, Hackenberg M, Aransay AM, Barrio R, Cantera R. (2012) Whole transcriptome analysis of a reversible neurodegenerative process in Drosophila reveals potential neuroprotective genes. BMC Genomics 13: 483. doi: 10.1186/1471-2164-13-483 22978642

28. Huang D, Sherman B, Lempicki R (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature protocols 4: 44–57. doi: 10.1038/nprot.2008.211 19131956

29. Huang D, Sherman B, Lempicki R (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37: 1–13. doi: 10.1093/nar/gkn923 19033363

30. modMine: flexible access to modENCODE data. Nucleic Acids Res. 2012 January; 40(D1): D1082–D1088

31. Hibi M, Lin A, Smeal T, Minden A, Karin M (1993) Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev 7: 2135–2148. 8224842

32. Szuperák M, Salah S, Meyer EJ, Nagarajan U, Ikmi A, Gibson MC (2011) Feedback regulation of Drosophila BMP signaling by the novel extracellular protein larval translucida. Development 138:715–24. doi: 10.1242/dev.059477 21266407

33. Ito K, Awano W, Suzuki K, Hiromi Y, Yamamoto D (1997) The Drosophils mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. Development 124: 761–771. 9043058

34. Martin-Blanco E, Gampel A, Ring J, Virdee K, Kirov N, Tolkovsky AM, Martinez-Arias A (1998) puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. Genes & Dev 12:557–570.

35. Dietzl G, Chen D, Schnorrer F, Su KC, Barinova Y, Fellner M, Gasser B, Kinsey K, Oppel S, Scheiblauer S, et al (2007) A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature, 448: 151–156. 17625558

36. Barrio R, de Celis JF, Bolshakov S, Kafatos FC (1999) Identification of regulatory regions driving the expression of the Drosophila spalt complex at different developmental stages. Dev Biol 215: 33–47. 10525348

37. Pierre S St., Ponting L, Stefancsik R, McQuilton P, Consortium F (2014) FlyBase 102—advanced approaches to interrogating FlyBase. Nucleic Acids Res 42: 80–88.

38. de Celis JF (1997) Expression and function of decapentaplegic and thick veins during the differentiation of the veins in the Drosophila wing. Development 124: 1007–1018. 9056776