Coordinating the morphogenesis-differentiation balance by tweaking the cytokinin-gibberellin equilibrium

Autoři: Alon Israeli aff001;  Yogev Burko aff001;  Sharona Shleizer-Burko aff001;  Iris Daphne Zelnik aff001;  Noa Sela aff002;  Mohammad R. Hajirezaei aff003;  Alisdair R. Fernie aff004;  Takayuki Tohge aff004;  Naomi Ori aff001;  Maya Bar aff001
Působiště autorů: The Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, Hebrew University, Rehovot, Israel aff001;  Department of Plant Pathology and Weed Research, Plant Protection Institute, Agricultural Research Organization, Volcani Institute, Rishon LeZion, Israel aff002;  Molecular Plant Nutrition, Department of Physiology and Cell Biology, Leibniz Institute of Plant Genetics and Crop Plant Research, Seeland, Germany aff003;  Max-Planck-Institute of Molecular Plant Physiology, Potsdam-Golm, Germany aff004
Vyšlo v časopise: Coordinating the morphogenesis-differentiation balance by tweaking the cytokinin-gibberellin equilibrium. PLoS Genet 17(4): e1009537. doi:10.1371/journal.pgen.1009537
Kategorie: Research Article


Morphogenesis and differentiation are important stages in organ development and shape determination. However, how they are balanced and tuned during development is not fully understood. In the compound leaved tomato, an extended morphogenesis phase allows for the initiation of leaflets, resulting in the compound form. Maintaining a prolonged morphogenetic phase in early stages of compound-leaf development in tomato is dependent on delayed activity of several factors that promote differentiation, including the CIN-TCP transcription factor (TF) LA, the MYB TF CLAU and the plant hormone Gibberellin (GA), as well as on the morphogenesis-promoting activity of the plant hormone cytokinin (CK). Here, we investigated the genetic regulation of the morphogenesis-differentiation balance by studying the relationship between LA, CLAU, TKN2, CK and GA. Our genetic and molecular examination suggest that LA is expressed earlier and more broadly than CLAU and determines the developmental context of CLAU activity. Genetic interaction analysis indicates that LA and CLAU likely promote differentiation in parallel genetic pathways. These pathways converge downstream on tuning the balance between CK and GA. Comprehensive transcriptomic analyses support the genetic data and provide insights into the broader molecular basis of differentiation and morphogenesis processes in plants.

Klíčová slova:

Graphs – Hyperexpression techniques – Leaf development – Leaves – Morphogenesis – Phenotypes – Tomatoes – Transcription factors


1. Wallingford JB, Morgan H, Spemann H, Mangold H, Ernst K. Aristotle, Buddhist scripture and embryology in ancient Mexico: building inclusion by re-thinking what counts as the history of developmental biology. 2021; 1–9. doi: 10.1242/dev.192062 33526415

2. Theophrastus. Enquiry into Plants 350–285 BC, trans Hort A. Harvard Univ Press, Cambridge, MA. 1916.

3. Van Speybroeck L, De Waele D, Van De Vijver G. Theories in Early Embryology. Ann NY Acad Sci. 2006;981: 7–49.

4. Munjal A, Philippe J, Munro E, Lecuit T. A self-organized biomechanical network drives shape changes during tissue morphogenesis. 2015. doi: 10.1038/nature14603 26214737

5. Sutherland A, Keller R, Lesko A. Seminars in Cell & Developmental Biology Convergent extension in mammalian morphogenesis. Seminars in Cell and Developmental Biology. 2020;100: 199–211. doi: 10.1016/j.semcdb.2019.11.002 31734039

6. Petit F, Sears KE, Ahituv N. Limb development: a paradigm of gene regulation. Nature. 2017;18: 245–258. doi: 10.1038/nrg.2016.167 28163321

7. Pałubicki W, Kokosza A, Burian A. Formal description of plant morphogenesis. Journal of Experimental Botany. 2019;70: 3601–3613. doi: 10.1093/jxb/erz210 31290543

8. Lintilhac PM. The problem of morphogenesis: unscripted biophysical control systems in plants. 2014; 25–36. doi: 10.1007/s00709-013-0522-y 23846861

9. Poethig RS. Leaf morphogenesis in flowering plants. The Plant Cell. 1997;9: 1077–1087. doi: 10.1105/tpc.9.7.1077 9254931

10. Bar M, Ori N. Leaf development and morphogenesis. Development (Cambridge, England). 2014;141: 4219–30. doi: 10.1242/dev.106195 25371359

11. Chitwood DH, Sinha NR. Evolutionary and Environmental Forces Sculpting Leaf Development. Current Biology. 2016;26: R297–R306. doi: 10.1016/j.cub.2016.02.033 27046820

12. Maugarny-Calès A, Laufs P. Getting leaves into shape: a molecular, cellular, environmental and evolutionary view. Development. 2018;145: 1–16. doi: 10.1242/dev.161646 29991476

13. Rodriguez RE, Debernardi JM, Palatnik JF. Morphogenesis of simple leaves: Regulation of leaf size and shape. Wiley Interdisciplinary Reviews: Developmental Biology. 2014;3: 41–57. doi: 10.1002/wdev.115 24902833

14. Du F, Guan C, Jiao Y. Molecular Mechanisms of Leaf Morphogenesis. Molecular plant. 2018;11: 1117–1134. doi: 10.1016/j.molp.2018.06.006 29960106

15. Bar M, Ori N. Compound leaf development in model plant species. Current opinion in plant biology. 2015;23: 61–9. doi: 10.1016/j.pbi.2014.10.007 25449728

16. Israeli A, Ben-Herzel O, Burko Y, Shwartz I, Ben-Gera H, Harpaz-Saad S, et al. Coordination of differentiation rate and local patterning in compound-leaf development. New Phytologist. 2020;229: 3558–3572. doi: 10.1111/nph.17124 33259078

17. Shwartz I, Levy M, Ori N, Bar M. Hormones in tomato leaf development. Developmental Biology. 2016;419: 132–142. doi: 10.1016/j.ydbio.2016.06.023 27339291

18. Naz AA, Raman S, Martinez CC, Sinha NR, Schmitz G, Theres K. Trifoliate encodes an MYB transcription factor that modulates leaf and shoot architecture in tomato. Proc Natl Acad Sci U S A. 2013;110: 2401–2406. doi: 10.1073/pnas.1214300110 23341595

19. Busch BL, Schmitz G, Rossmann S, Piron F, Ding J, Bendahmane A, et al. Shoot branching and leaf dissection in tomato are regulated by homologous gene modules. The Plant Cell. 2011;23: 3595–609. doi: 10.1105/tpc.111.087981 22039213

20. Shani E, Ben-Gera H, Shleizer-Burko S, Burko Y, Weiss D, Ori N. Cytokinin regulates compound leaf development in tomato. The Plant Cell. 2010;22: 3206–3217. doi: 10.1105/tpc.110.078253 20959562

21. Yanai O, Shani E, Russ D, Ori N. Gibberellin partly mediates LANCEOLATE activity in tomato. The Plant journal. 2011;68: 571–582. doi: 10.1111/j.1365-313X.2011.04716.x 21771122

22. Bar M, Israeli A, Levy M, Ben Gera H, Jiménez-Gómez JM, Kouril S, et al. CLAUSA Is a MYB Transcription Factor That Promotes Leaf Differentiation by Attenuating Cytokinin Signaling. The Plant Cell. 2016;28: 1602–15. doi: 10.1105/tpc.16.00211 27385816

23. Hajheidari M, Wang Y, Bhatia N, Huijser P, Gan X, Tsiantis M. Autoregulation of RCO by Low-Affinity Binding Modulates Cytokinin Action and Shapes Leaf Article. Current Biology. 2019;29: 1–10. doi: 10.1016/j.cub.2018.11.016 30581019

24. Furumizu C, Alvarez JP, Sakakibara K, Bowman JL. Antagonistic Roles for KNOX1 and KNOX2 Genes in Patterning the Land Plant Body Plan Following an Ancient Gene Duplication. PLoS Genetics. 2015;11(2): e1004980. doi: 10.1371/journal.pgen.1004980 25671434

25. Raman S, Greb T, Peaucelle A, Blein T, Laufs P, Theres K. Interplay of miR164, CUP-SHAPED COTYLEDON genes and LATERAL SUPPRESSOR controls axillary meristem formation in Arabidopsis thaliana. Plant Journal. 2008;55: 65–76. doi: 10.1111/j.1365-313X.2008.03483.x 18346190

26. Shani E, Yanai O, Ori N. The role of hormones in shoot apical meristem function. Current opinion in plant biology. 2006;9: 484–9. doi: 10.1016/j.pbi.2006.07.008 16877025

27. Fleishon S, Shani E, Ori N, Weiss D. Negative reciprocal interactions between gibberellin and cytokinin in tomato. The New phytologist. 2011;190: 609–17. doi: 10.1111/j.1469-8137.2010.03616.x 21244434

28. Nath U, Crawford BCW, Carpenter R, Coen E. Genetic Control of Surface Curvature. Science. 2003;299: 1404–1408. doi: 10.1126/science.1079354 12610308

29. Efroni I, Blum E, Goldshmidt A, Eshed Y. A protracted and dynamic maturation schedule underlies Arabidopsis leaf development. The Plant Cell. 2008;20: 2293–2306. doi: 10.1105/tpc.107.057521 18805992

30. Blein T, Pautot V, Laufs P. Combinations of Mutations Sufficient to Alter Arabidopsis Leaf Dissection. Plants. 2013;2: 230–247. Available: doi: 10.3390/plants2020230 27137374

31. Schommer C, Debernardi JM, Bresso EG, Rodriguez RE, Palatnik JF. Repression of cell proliferation by miR319-regulated TCP4. Molecular Plant. 2014;7: 1533–1544. doi: 10.1093/mp/ssu084 25053833

32. Koyama T, Sato F, Ohme-Takagi M. Roles of miR319 and TCP transcription factors in leaf development. Plant Physiology. 2017;175: pp.00732.2017. doi: 10.1104/pp.17.00732 28842549

33. Ori N, Cohen AR, Etzioni A, Brand A, Yanai O, Shleizer S, et al. Regulation of LANCEOLATE by miR319 is required for compound-leaf development in tomato. Nature genetics. 2007;39: 787–791. doi: 10.1038/ng2036 17486095

34. Shleizer-Burko S, Burko Y, Ben-Herzel O, Ori N. Dynamic growth program regulated by LANCEOLATE enables flexible leaf patterning. Development (Cambridge, England). 2011;138: 695–704. doi: 10.1242/dev.056770 21228002

35. Ballester P, Navarrete-Gomez M, Carbonero P, Onate-Sanchez L, Ferrandiz C. Leaf expansion in Arabidopsis is controlled by a TCP-NGA regulatory module likely conserved in distantly related species. Physiologia Plantarum. 2015;155: 21–32. doi: 10.1111/ppl.12327 25625546

36. Challa KR, Rath M, Nath U. The CIN-TCP transcription factors promote commitment to differentiation in Arabidopsis leaf pavement cells via both auxin-dependent and independent pathways. PLoS Genetics. 2019;15: 1–30. doi: 10.1371/journal.pgen.1007988 30742619

37. Palatnik JF, Allen E, Wu X, Schommer C, Schwab R, Carrington JC, et al. Control of leaf morphogenesis by microRNAs. Nature. 2003;425: 257–263. doi: 10.1038/nature01958 12931144

38. Dengler NG. Comparison of Leaf Development in Normal (+/+), Entire (e/e), and Lanceolate (La/+) Plants of Tomato, Lycopersicon esculentum “Ailsa Craig.” Botanical Gazette. 1984;145: 66–77.

39. Mathan DS, Jenkins JA. A Morphogenetic Study of Lanceolate, A Leaf-Shape Mutant in the Tomato. American Journal of Botany. 1962;49: 504–514.

40. Koyama T, Furutani M, Tasaka M, Ohme-Takagi M. TCP transcription factors control the morphology of shoot lateral organs via negative regulation of the expression of boundary-specific genes in Arabidopsis. The Plant Cell. 2007;19: 473–84. doi: 10.1105/tpc.106.044792 17307931

41. Efroni I, Han S-K, Kim HJ, Wu M-F, Steiner E, Birnbaum KD, et al. Regulation of Leaf Maturation by Chromatin-Mediated Modulation of Cytokinin Responses. Developmental Cell. 2013;24: 438–445. doi: 10.1016/j.devcel.2013.01.019 23449474

42. Avivi Y, Lev-yadun S, Morozova N, Libs L, Williams L, Zhao J, et al. Clausa, a Tomato Mutant with a Wide Range of Phenotypic Perturbations, Displays a Cell Type- Dependent Expression of the Homeobox Gene LeT6 / TKn2 1. Plant physiology. 2000;124: 541–551. doi: 10.1104/pp.124.2.541 11027705

43. Bar M, Ben-Herzel O, Kohay H, Shtein I, Ori N. CLAUSA restricts tomato leaf morphogenesis and GOBLET expression. The Plant journal 2015;83: 888–902. doi: 10.1111/tpj.12936 26189897

44. Jasinski S, Tattersall A, Piazza P, Hay A, Martinez-Garcia JF, Schmitz G, et al. PROCERA encodes a DELLA protein that mediates control of dissected leaf form in tomato. The Plant journal 2008;56: 603–12. doi: 10.1111/j.1365-313X.2008.03628.x 18643984

45. Bharathan G, Goliber TE, Moore C, Kessler S, Pham T, Sinha NR. Homologies in Leaf Form Inferred from KNOXI Gene Expression During Development. Science. 2002;296: 1858–1860. doi: 10.1126/science.1070343 12052958

46. Hake S, Smith HMS, Holtan H, Magnani E, Mele G, Ramirez J. the Role of Knox Genes in Plant Development #. Annu Rev Cell Dev Biol. 2004;20: 125–51. doi: 10.1146/annurev.cellbio.20.031803.093824 15473837

47. Hay A, Tsiantis M. A KNOX family TALE. Current Opinion in Plant Biology. 2009;12: 593–598. doi: 10.1016/j.pbi.2009.06.006 19632142

48. Shani E, Burko Y, Ben-Yaakov L, Berger Y, Amsellem Z, Goldshmidt A, et al. Stage-specific regulation of Solanum lycopersicum leaf maturation by class 1 KNOTTED1-LIKE HOMEOBOX proteins. The Plant Cell. 2009;21: 3078–3092. doi: 10.1105/tpc.109.068148 19820191

49. Kimura S, Koenig D, Kang J, Yoong FY, Sinha N. Natural Variation in Leaf Morphology Results from Mutation of a Novel KNOX Gene. Current Biology. 2008;18: 672–677. doi: 10.1016/j.cub.2008.04.008 18424140

50. Janssen B-J, Lund L, Sinha N. Overexpression of a Homeobox Gene, LeT6, Reveals Indeterminate Features in the Tomato Compound Leaf1. Plant physiology. 1998;117: 771–786. doi: 10.1104/pp.117.3.771 9662520

51. Zhou C, Han L, Li G, Chai M, Fu C, Cheng X, et al. STM/BP-Like KNOXI Is Uncoupled from ARP in the Regulation of Compound Leaf Development in Medicago truncatula. The Plant Cell. 2014/05/02. 2014;26: 1464–1479. doi:tpc.114.123885 [pii] doi: 10.1105/tpc.114.123885 24781113

52. Jasinski S, Piazza P, Craft J, Hay A, Woolley L, Rieu I, et al. KNOX Action in Arabidopsis Is Mediated by Coordinate Regulation of Cytokinin and Gibberellin Activities. 2005;15: 1560–1565. doi: 10.1016/j.cub.2005.07.023 16139211

53. Yanai O, Shani E, Dolezal K, Tarkowski P, Sablowski R, Sandberg G, et al. Arabidopsis KNOXI proteins activate cytokinin biosynthesis. Current biology: CB. 2005;15: 1566–71. doi: 10.1016/j.cub.2005.07.060 16139212

54. Bolduc N, Hake S. The maize transcription factor KNOTTED1 directly regulates the gibberellin catabolism gene ga2ox1. The Plant Cell. 2009;21: 1647–58. doi: 10.1105/tpc.109.068221 19567707

55. Sakamoto T, Kamiya N, Ueguehi-Tanaka M, Iwahori S, Matsuoka M. KNOX homeodomain protein directly suppresses the expression of a gibberellin biosynthetic gene in the tobacco shoot apical meristem. Genes and Development. 2001;15: 581–590. doi: 10.1101/gad.867901 11238378

56. Jasinski S, Kaur H, Tattersall A. Negative regulation of KNOX expression in tomato leaves. Planta. 2007;226: 1255–1263. doi: 10.1007/s00425-007-0572-5 17628827

57. Wang Y, Chen R. Regulation of Compound Leaf Development. Plants. 2013;3: 1–17. Available: doi: 10.3390/plants3010001 27135488

58. Kang J, Sinha N. Leaflet initiation is temporally and spatially separated in simple and complex tomato (Solanum lycopersicum) leaf mutants: a developmental\ranalysis. Botany. 2010;88: 710–724. doi: 10.1139/B10-051

59. Burko Y, Shleizer-Burko S, Yanai O, Shwartz I, Zelnik ID, Jacob-Hirsch J, et al. A role for APETALA1/fruitfull transcription factors in tomato leaf development. The Plant Cell. 2013. pp. 2070–83. doi: 10.1105/tpc.113.113035 23771895

60. Chen JJ, Janssen BJ, Williams A, Sinha N. A gene fusion at a homeobox locus: alterations in leaf shape and implications for morphological evolution. The Plant Cell. 1997;9: 1289–1304. doi: 10.1105/tpc.9.8.1289 9286107

61. Hareven D, Gutfinger T, Parnis A, Eshed Y, Lifschitz E. The making of a compound leaf: Genetic manipulation of leaf architecture in tomato. Cell. 1996;84: 735–744. doi: 10.1016/s0092-8674(00)81051-x 8625411

62. Parnis A, Cohen O, Gutfinger T, Hareven D, Zamir D, Lifschitz E. The dominant developmental mutants of tomato, Mouse-Ear and Curl, are associated with distinct modes of abnormal transcriptional regulation of a Knotted gene. The Plant Cell. 1997;9: 2143–2158. doi: 10.1105/tpc.9.12.2143 9437860

63. Hay A, Tsiantis M. KNOX genes: versatile regulators of plant development and diversity. Development (Cambridge, England). 2010;137: 3153–3165. doi: 10.1242/dev.030049 20823061

64. Hay A, Kaur H, Phillips A, Hedden P, Hake S, Tsiantis M. The gibberellin pathway mediates KNOTTED1-type homeobox function in plants with different body plans. Current Biology. 2002;12: 1557–1565. doi: 10.1016/s0960-9822(02)01125-9 12372247

65. Koltai H, Bird DMK. Epistatic repression of PHANTASTICA and class 1 KNOTTED genes is uncoupled in tomato. Plant Journal. 2000;22: 455–459. doi: 10.1046/j.1365-313X.2000.00754.x 10849361

66. Silva GFF, Silva EM, Correa JPO, Vicente MH, Jiang N, Notini MM, et al. Tomato floral induction and flower development are orchestrated by the interplay between gibberellin and two unrelated microRNA-controlled modules. New Phytologist. 2019;221: 1328–1344. doi: 10.1111/nph.15492 30238569

67. Weiss D, Ori N. Mechanisms of cross talk between gibberellin and other hormones. Plant physiology. 2007;144: 1240–6. doi: 10.1104/pp.107.100370 17616507

68. Steiner E, Israeli A, Gupta R, Shwartz I, Nir I, Markus ML, et al. Characterization of the cytokinin sensor TCSv2 in arabidopsis and tomato. Plant Methods. 2020;16: 152. doi: 10.1186/s13007-020-00694-2 33292327

69. Greenboim-Wainberg Y, Maymon I, Borochov R, Alvarez J, Olszewski N, Ori N, et al. Cross talk between gibberellin and cytokinin: the Arabidopsis GA response inhibitor SPINDLY plays a positive role in cytokinin signaling. The Plant Cell. 2005;17: 92–102. doi: 10.1105/tpc.104.028472 15608330

70. Gupta R, Pizarro L, Leibman-Markus M, Marash I, Bar M. Cytokinin response induces immunity and fungal pathogen resistance, and modulates trafficking of the PRR LeEIX2 in tomato. Molecular Plant Pathology. 2020;21: 1287–1306. doi: 10.1111/mpp.12978 32841497

71. Ichihashi Y, Aguilar-Martínez JA, Farhi M, Chitwood DH, Kumar R, Millon L V, et al. Evolutionary developmental transcriptomics reveals a gene network module regulating interspecific diversity in plant leaf shape. Proceedings of the National Academy of Sciences of the United States of America. 2014;111: E2616–E2621. doi: 10.1073/pnas.1402835111 24927584

72. Shani E, Ben-Gera H, Shleizer-Burko S, Burko Y, Weiss D, Ori N. Cytokinin Regulates Compound Leaf Development in Tomato. The Plant Cell. 2010/10/21. 2010;22: 3206–3217. doi:tpc.110.078253 [pii] doi: 10.1105/tpc.110.078253 20959562

73. Scofield S, Dewitte W, Nieuwland J, Murray JAH. The Arabidopsis homeobox gene SHOOT MERISTEMLESS has cellular and meristem-organisational roles with differential requirements for cytokinin and CYCD3 activity. The Plant Journal. 2013;75: 53–66. doi: 10.1111/tpj.12198 23573875

74. Maltnan DS, Jenkins J a LB-PBSR 20. A morphogenetic study of Lanceolate, a leaf shape mutant in tomato. Am J Bot. 1962;49: 504–514.

75. Floyd SK, Bowman JL. Gene expression patterns in seed plant shoot meristems and leaves: Homoplasy or homology? Journal of Plant Research. 2010;123: 43–55. doi: 10.1007/s10265-009-0256-2 19784716

76. Menda N, Semel Y, Peled D, Eshed Y, Zamir D. In silico screening of a saturated mutation library of tomato. The Plant journal 2004;38: 861–872. doi: 10.1111/j.1365-313X.2004.02088.x 15144386

77. Nir I, Shohat H, Panizel I, Olszewski NE, Aharoni A, Weiss D. The Tomato DELLA Protein PROCERA Acts in Guard Cells to Promote Stomatal Closure. The Plant Cell. 2017; tpc.00542.2017. doi: 10.1105/tpc.17.00542 29150547

78. Steiner E, Livne S, Kobinson-Katz T, Tal L, Pri-Tal O, Mosquna A, et al. The Putative O-Linked N-Acetylglucosamine Transferase SPINDLY Inhibits Class I TCP Proteolysis to Promote Sensitivity to Cytokinin. Plant physiology. 2016;171: 1485–94. doi: 10.1104/pp.16.00343 27208284

79. Zürcher E, Tavor-Deslex D, Lituiev D, Enkerli K, Tarr PT, Müller B. A robust and sensitive synthetic sensor to monitor the transcriptional output of the cytokinin signaling network in planta. Plant physiology. 2013;161: 1066–75. doi: 10.1104/pp.112.211763 23355633

80. Šimura J, Antoniadi I, Široká J, Tarkowská D, Strnad M, Ljung K, et al. Plant Hormonomics: Multiple Phytohormone Profiling by. Plant Physiology. 2018;177: 476–489. doi: 10.1104/pp.18.00293 29703867

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