The Drosophila FUS ortholog cabeza promotes adult founder myoblast selection by Xrp1-dependent regulation of FGF signaling

English version

Autoři: Marica Catinozzi ^aff001; Moushami Mallik ^aff001; Marie Frickenhaus ^aff002; Marije Been ^aff001; Céline Sijlmans ^aff001; Divita Kulshrestha ^aff001; Ioannis Alexopoulos ^aff004; Manuela Weitkunat ^aff005; Frank Schnorrer ^aff005; Erik Storkebaum ^aff001
Působiště autorů: Department of Molecular Neurobiology, Donders Institute for Brain, Cognition and Behaviour and Faculty of Science, Radboud University, Nijmegen, Netherlands ^aff001; Molecular Neurogenetics Laboratory, Max Planck Institute for Molecular Biomedicine, Muenster, Germany ^aff002; Faculty of Medicine, University of Muenster, Muenster, Germany ^aff003; General Instruments Department, Faculty of Science, Radboud University, Nijmegen, Netherlands ^aff004; Muscle Dynamics Group, Max Planck Institute of Biochemistry, Martinsried, Germany ^aff005; Aix Marseille University, CNRS, IBDM, Marseille, France ^aff006
Vyšlo v časopise: The Drosophila FUS ortholog cabeza promotes adult founder myoblast selection by Xrp1-dependent regulation of FGF signaling. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008731
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008731

Souhrn

The number of adult myofibers in Drosophila is determined by the number of founder myoblasts selected from a myoblast pool, a process governed by fibroblast growth factor (FGF) signaling. Here, we show that loss of cabeza (caz) function results in a reduced number of adult founder myoblasts, leading to a reduced number and misorientation of adult dorsal abdominal muscles. Genetic experiments revealed that loss of caz function in both adult myoblasts and neurons contributes to caz mutant muscle phenotypes. Selective overexpression of the FGF receptor Htl or the FGF receptor-specific signaling molecule Stumps in adult myoblasts partially rescued caz mutant muscle phenotypes, and Stumps levels were reduced in caz mutant founder myoblasts, indicating FGF pathway deregulation. In both adult myoblasts and neurons, caz mutant muscle phenotypes were mediated by increased expression levels of Xrp1, a DNA-binding protein involved in gene expression regulation. Xrp1-induced phenotypes were dependent on the DNA-binding capacity of its AT-hook motif, and increased Xrp1 levels in founder myoblasts reduced Stumps expression. Thus, control of Xrp1 expression by Caz is required for regulation of Stumps expression in founder myoblasts, resulting in correct founder myoblast selection.

Klíčová slova:

Abdominal muscles – Immunostaining – Motor neurons – Muscle functions – Myoblasts – Neurons – Phenotypes – Pupae

Zdroje

1. Currie DA, Bate M. The development of adult abdominal muscles in Drosophila: myoblasts express twist and are associated with nerves. Development. 1991;113(1):91–102. Epub 1991/09/01. 1765011.

2. Truman JW. Metamorphosis of the central nervous system of Drosophila. J Neurobiol. 1990;21(7):1072–84. Epub 1990/10/01. doi: 10.1002/neu.480210711 1979610.

3. Broadie KS, Bate M. The development of adult muscles in Drosophila: ablation of identified muscle precursor cells. Development. 1991;113(1):103–18. Epub 1991/09/01. 1764988.

4. Dutta D, Anant S, Ruiz-Gomez M, Bate M, VijayRaghavan K. Founder myoblasts and fibre number during adult myogenesis in Drosophila. Development. 2004;131(15):3761–72. Epub 2004/07/21. doi: 10.1242/dev.01249 15262890.

5. Baker R, Schubiger G. Autonomous and nonautonomous Notch functions for embryonic muscle and epidermis development in Drosophila. Development. 1996;122(2):617–26. Epub 1996/02/01. 8625813.

6. Dutta D, Shaw S, Maqbool T, Pandya H, Vijayraghavan K. Drosophila Heartless acts with Heartbroken/Dof in muscle founder differentiation. PLoS Biol. 2005;3(10):e337. Epub 2005/10/07. doi: 10.1371/journal.pbio.0030337 16207075; PubMed Central PMCID: PMC1197288.

7. Schwartz JC, Cech TR, Parker RR. Biochemical Properties and Biological Functions of FET Proteins. Annu Rev Biochem. 2015;84 : 355–79. doi: 10.1146/annurev-biochem-060614-034325 25494299.

8. Ling SC, Polymenidou M, Cleveland DW. Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron. 2013;79(3):416–38. doi: 10.1016/j.neuron.2013.07.033 23931993.

9. Frickenhaus M, Wagner M, Mallik M, Catinozzi M, Storkebaum E. Highly efficient cell-type-specific gene inactivation reveals a key function for the Drosophila FUS homolog cabeza in neurons. Sci Rep. 2015;5 : 9107. doi: 10.1038/srep09107 25772687.

10. Mallik M, Catinozzi M, Hug CB, Zhang L, Wagner M, Bussmann J, et al. Xrp1 genetically interacts with the ALS-associated FUS orthologue caz and mediates its toxicity. J Cell Biol. 2018;217(11):3947–64. Epub 2018/09/14. doi: 10.1083/jcb.201802151 30209068; PubMed Central PMCID: PMC6219715.

11. Orfanos Z, Sparrow JC. Myosin isoform switching during assembly of the Drosophila flight muscle thick filament lattice. J Cell Sci. 2013;126(Pt 1):139–48. Epub 2012/11/28. doi: 10.1242/jcs.110361 23178940.

12. Clyne PJ, Brotman JS, Sweeney ST, Davis G. Green fluorescent protein tagging Drosophila proteins at their native genomic loci with small P elements. Genetics. 2003;165(3):1433–41. Epub 2003/12/12. 14668392; PubMed Central PMCID: PMC1462835.

13. Weitkunat M, Kaya-Copur A, Grill SW, Schnorrer F. Tension and force-resistant attachment are essential for myofibrillogenesis in Drosophila flight muscle. Curr Biol. 2014;24(7):705–16. Epub 2014/03/19. doi: 10.1016/j.cub.2014.02.032 24631244.

14. Bainbridge SP, Bownes M. Staging the metamorphosis of Drosophila melanogaster. J Embryol Exp Morphol. 1981;66 : 57–80. Epub 1981/12/01. 6802923.

15. Wang JW, Brent JR, Tomlinson A, Shneider NA, McCabe BD. The ALS-associated proteins FUS and TDP-43 function together to affect Drosophila locomotion and life span. J Clin Invest. 2011;121(10):4118–26. doi: 10.1172/JCI57883 21881207; PubMed Central PMCID: PMC3195475.

16. Vincent S, Wilson R, Coelho C, Affolter M, Leptin M. The Drosophila protein Dof is specifically required for FGF signaling. Mol Cell. 1998;2(4):515–25. Epub 1998/11/11. doi: 10.1016/s1097-2765(00)80151-3 9809073.

17. Akdemir F, Christich A, Sogame N, Chapo J, Abrams JM. p53 directs focused genomic responses in Drosophila. Oncogene. 2007;26(36):5184–93. Epub 2007/02/22. doi: 10.1038/sj.onc.1210328 17310982.

18. Francis MJ, Roche S, Cho MJ, Beall E, Min B, Panganiban RP, et al. Drosophila IRBP bZIP heterodimer binds P-element DNA and affects hybrid dysgenesis. Proc Natl Acad Sci U S A. 2016;113(46):13003–8. Epub 2016/11/02. doi: 10.1073/pnas.1613508113 27799520; PubMed Central PMCID: PMC5135294.

19. Lee CH, Kiparaki M, Blanco J, Folgado V, Ji Z, Kumar A, et al. A Regulatory Response to Ribosomal Protein Mutations Controls Translation, Growth, and Cell Competition. Dev Cell. 2018;46(4):456–69 e4. Epub 2018/08/07. doi: 10.1016/j.devcel.2018.07.003 30078730; PubMed Central PMCID: PMC6261318.

20. Baillon L, Germani F, Rockel C, Hilchenbach J, Basler K. Xrp1 is a transcription factor required for cell competition-driven elimination of loser cells. Scientific reports. 2018;8(1):17712. Epub 2018/12/12. doi: 10.1038/s41598-018-36277-4 30531963; PubMed Central PMCID: PMC6286310.

21. Boulan L, Andersen D, Colombani J, Boone E, Leopold P. Inter-Organ Growth Coordination Is Mediated by the Xrp1-Dilp8 Axis in Drosophila. Dev Cell. 2019;49(5):811–8 e4. Epub 2019/04/23. doi: 10.1016/j.devcel.2019.03.016 31006647.

22. Currie DA, Bate M. Innervation is essential for the development and differentiation of a sex-specific adult muscle in Drosophila melanogaster. Development. 1995;121(8):2549–57. Epub 1995/08/01. 7671818.

23. Lawrence PA, Johnston P. The muscle pattern of a segment of Drosophila may be determined by neurons and not by contributing myoblasts. Cell. 1986;45(4):505–13. Epub 1986/05/23. doi: 10.1016/0092-8674(86)90282-5 3085954.

24. Deng H, Gao K, Jankovic J. The role of FUS gene variants in neurodegenerative diseases. Nature Reviews Neurology. 2014;10(6):337–48. doi: 10.1038/nrneurol.2014.78 WOS:000337232600007. 24840975

25. Dobrowolny G, Aucello M, Rizzuto E, Beccafico S, Mammucari C, Boncompagni S, et al. Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab. 2008;8(5):425–36. Epub 2008/12/03. doi: 10.1016/j.cmet.2008.09.002 19046573.

26. Wong M, Martin LJ. Skeletal muscle-restricted expression of human SOD1 causes motor neuron degeneration in transgenic mice. Hum Mol Genet. 2010;19(11):2284–302. Epub 2010/03/13. doi: 10.1093/hmg/ddq106 20223753; PubMed Central PMCID: PMC2865380.

27. Miller TM, Kim SH, Yamanaka K, Hester M, Umapathi P, Arnson H, et al. Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2006;103(51):19546–51. Epub 2006/12/14. doi: 10.1073/pnas.0609411103 17164329; PubMed Central PMCID: PMC1748262.

28. Towne C, Raoul C, Schneider BL, Aebischer P. Systemic AAV6 delivery mediating RNA interference against SOD1: neuromuscular transduction does not alter disease progression in fALS mice. Mol Ther. 2008;16(6):1018–25. Epub 2008/04/17. doi: 10.1038/mt.2008.73 18414477.

29. Picchiarelli G, Demestre M, Zuko A, Been M, Higelin J, Dieterle S, et al. FUS-mediated regulation of acetylcholine receptor transcription at neuromuscular junctions is compromised in amyotrophic lateral sclerosis. Nature Neuroscience. 2019;22(11):1793–805. doi: 10.1038/s41593-019-0498-9 WOS:000493396600008. 31591561

30. Scekic-Zahirovic J, Oussini HE, Mersmann S, Drenner K, Wagner M, Sun Y, et al. Motor neuron intrinsic and extrinsic mechanisms contribute to the pathogenesis of FUS-associated amyotrophic lateral sclerosis. Acta Neuropathol. 2017;133(6):887–906. Epub 2017/03/01. doi: 10.1007/s00401-017-1687-9 28243725; PubMed Central PMCID: PMC5427169.

31. Scekic-Zahirovic J, Sendscheid O, El Oussini H, Jambeau M, Sun Y, Mersmann S, et al. Toxic gain of function from mutant FUS protein is crucial to trigger cell autonomous motor neuron loss. The EMBO journal. 2016;35(10):1077–97. doi: 10.15252/embj.201592559 26951610; PubMed Central PMCID: PMC4868956.

32. Sharma A, Lyashchenko AK, Lu L, Nasrabady SE, Elmaleh M, Mendelsohn M, et al. ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function. Nature communications. 2016;7 : 10465. doi: 10.1038/ncomms10465 26842965.

33. Williams AH, Valdez G, Moresi V, Qi X, McAnally J, Elliott JL, et al. MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science. 2009;326(5959):1549–54. Epub 2009/12/17. doi: 10.1126/science.1181046 20007902; PubMed Central PMCID: PMC2796560.

34. Sen A, Yokokura T, Kankel MW, Dimlich DN, Manent J, Sanyal S, et al. Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling. J Cell Biol. 2011;192(3):481–95. Epub 2011/02/09. doi: 10.1083/jcb.201004016 21300852; PubMed Central PMCID: PMC3101100.

35. Faravelli I, Nizzardo M, Comi GP, Corti S. Spinal muscular atrophy—recent therapeutic advances for an old challenge. Nature reviews Neurology. 2015;11(6):351–9. Epub 2015/05/20. doi: 10.1038/nrneurol.2015.77 25986506.

36. Sun S, Ling SC, Qiu J, Albuquerque CP, Zhou Y, Tokunaga S, et al. ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP. Nature communications. 2015;6 : 6171. Epub 2015/01/28. doi: 10.1038/ncomms7171 25625564; PubMed Central PMCID: PMC4338613.

37. Groen EJ, Fumoto K, Blokhuis AM, Engelen-Lee J, Zhou Y, van den Heuvel DM, et al. ALS-associated mutations in FUS disrupt the axonal distribution and function of SMN. Hum Mol Genet. 2013;22(18):3690–704. Epub 2013/05/18. doi: 10.1093/hmg/ddt222 23681068.

38. Tsuiji H, Iguchi Y, Furuya A, Kataoka A, Hatsuta H, Atsuta N, et al. Spliceosome integrity is defective in the motor neuron diseases ALS and SMA. EMBO Mol Med. 2013;5(2):221–34. Epub 2012/12/21. doi: 10.1002/emmm.201202303 23255347; PubMed Central PMCID: PMC3569639.

39. Yamazaki T, Chen S, Yu Y, Yan B, Haertlein TC, Carrasco MA, et al. FUS-SMN protein interactions link the motor neuron diseases ALS and SMA. Cell Rep. 2012;2(4):799–806. Epub 2012/10/02. doi: 10.1016/j.celrep.2012.08.025 23022481; PubMed Central PMCID: PMC3483417.

40. Roy S, VijayRaghavan K. Homeotic genes and the regulation of myoblast migration, fusion, and fibre-specific gene expression during adult myogenesis in Drosophila. Development. 1997;124(17):3333–41. Epub 1997/10/06. 9310328.

41. Ruiz-Gomez M, Coutts N, Price A, Taylor MV, Bate M. Drosophila dumbfounded: a myoblast attractant essential for fusion. Cell. 2000;102(2):189–98. Epub 2000/08/16. doi: 10.1016/s0092-8674(00)00024-6 10943839.

42. 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(7):676–82. Epub 2012/06/30. doi: 10.1038/nmeth.2019 22743772; PubMed Central PMCID: PMC3855844.

43. Immanuel D, Zinszner H, Ron D. Association of SARFH (sarcoma-associated RNA-binding fly homolog) with regions of chromatin transcribed by RNA polymerase II. Mol Cell Biol. 1995;15(8):4562–71. Epub 1995/08/01. doi: 10.1128/mcb.15.8.4562 7623847; PubMed Central PMCID: PMC230696.

Článek The plant mobile domain proteins MAIN and MAIL1 interact with the phosphatase PP7L to regulate gene expression and silence transposable elements in Arabidopsis thaliana

Článek High expression in maize pollen correlates with genetic contributions to pollen fitness as well as with coordinated transcription from neighboring transposable elements

Článek XPF-ERCC1 protects liver, kidney and blood homeostasis outside the canonical excision repair pathways

Článek The nanophthalmos protein TMEM98 inhibits MYRF self-cleavage and is required for eye size specification

Článek Is imprinting the result of “friendly fire” by the host defense system?

Článek XPF–ERCC1: Linchpin of DNA crosslink repair

Článek A missense variant in Mitochondrial Amidoxime Reducing Component 1 gene and protection against liver disease

Článek Deconstructing cerebellar development cell by cell

Článek Variants encoding a restricted carboxy-terminal domain of SLC12A2 cause hereditary hearing loss in humans

Článek Molecular genetics of maternally-controlled cell divisions

Článek Parallelism in eco-morphology and gene expression despite variable evolutionary and genomic backgrounds in a Holarctic fish

Článek An integrated analysis of cell-type specific gene expression reveals genes regulated by REVOLUTA and KANADI1 in the Arabidopsis shoot apical meristem