The bZIP Transcription Factor MoAP1 Mediates the Oxidative Stress Response and Is Critical for Pathogenicity of the Rice Blast Fungus
Saccharomyces cerevisiae Yap1 protein is an AP1-like transcription factor involved in the regulation of the oxidative stress response. An ortholog of Yap1, MoAP1, was recently identified from the rice blast fungus Magnaporthe oryzae genome. We found that MoAP1 is highly expressed in conidia and during invasive hyphal growth. The Moap1 mutant was sensitive to H2O2, similar to S. cerevisiae yap1 mutants, and MoAP1 complemented Yap1 function in resistance to H2O2, albeit partially. The Moap1 mutant also exhibited various defects in aerial hyphal growth, mycelial branching, conidia formation, the production of extracellular peroxidases and laccases, and melanin pigmentation. Consequently, the Moap1 mutant was unable to infect the host plant. The MoAP1-eGFP fusion protein is localized inside the nucleus upon exposure to H2O2, suggesting that MoAP1 also functions as a redox sensor. Moreover, through RNA sequence analysis, many MoAP1-regulated genes were identified, including several novel ones that were also involved in pathogenicity. Disruption of respective MGG_01662 (MoAAT) and MGG_02531 (encoding hypothetical protein) genes did not result in any detectable changes in conidial germination and appressorium formation but reduced pathogenicity, whereas the mutant strains of MGG_01230 (MoSSADH) and MGG_15157 (MoACT) showed marketed reductions in aerial hyphal growth, mycelial branching, and loss of conidiation as well as pathogenicity, similar to the Moap1 mutant. Taken together, our studies identify MoAP1 as a positive transcription factor that regulates transcriptions of MGG_01662, MGG_02531, MGG_01230, and MGG_15157 that are important in the growth, development, and pathogenicity of M. oryzae.
Vyšlo v časopise:
The bZIP Transcription Factor MoAP1 Mediates the Oxidative Stress Response and Is Critical for Pathogenicity of the Rice Blast Fungus. PLoS Pathog 7(2): e32767. doi:10.1371/journal.ppat.1001302
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Research Article
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https://doi.org/10.1371/journal.ppat.1001302
Souhrn
Saccharomyces cerevisiae Yap1 protein is an AP1-like transcription factor involved in the regulation of the oxidative stress response. An ortholog of Yap1, MoAP1, was recently identified from the rice blast fungus Magnaporthe oryzae genome. We found that MoAP1 is highly expressed in conidia and during invasive hyphal growth. The Moap1 mutant was sensitive to H2O2, similar to S. cerevisiae yap1 mutants, and MoAP1 complemented Yap1 function in resistance to H2O2, albeit partially. The Moap1 mutant also exhibited various defects in aerial hyphal growth, mycelial branching, conidia formation, the production of extracellular peroxidases and laccases, and melanin pigmentation. Consequently, the Moap1 mutant was unable to infect the host plant. The MoAP1-eGFP fusion protein is localized inside the nucleus upon exposure to H2O2, suggesting that MoAP1 also functions as a redox sensor. Moreover, through RNA sequence analysis, many MoAP1-regulated genes were identified, including several novel ones that were also involved in pathogenicity. Disruption of respective MGG_01662 (MoAAT) and MGG_02531 (encoding hypothetical protein) genes did not result in any detectable changes in conidial germination and appressorium formation but reduced pathogenicity, whereas the mutant strains of MGG_01230 (MoSSADH) and MGG_15157 (MoACT) showed marketed reductions in aerial hyphal growth, mycelial branching, and loss of conidiation as well as pathogenicity, similar to the Moap1 mutant. Taken together, our studies identify MoAP1 as a positive transcription factor that regulates transcriptions of MGG_01662, MGG_02531, MGG_01230, and MGG_15157 that are important in the growth, development, and pathogenicity of M. oryzae.
Zdroje
1. DokeN
MiuraY
SanchezLM
ParkHJ
NoritakeT
1996 The oxidative burst protects plants against pathogen attack: mechanism and role as an emergency signal for plant bio-defence-a review. Gene 179 45 51
2. ApostolI
HeinsteinPF
LowPS
1989 Rapid Stimulation of an Oxidative Burst during Elicitation of Cultured Plant Cells: Role in Defense and Signal Transduction. Plant Physiol 90 109 116
3. ChenSX
SchopferP
1999 Hydroxyl-radical production in physiological reactions. A novel function of peroxidase. Eur J Biochem 260 726 735
4. TorresMA
DanglJL
2005 Functions of the respiratory burst oxidase in biotic interactions, abiotic stress and development. Curr Opin Plant Biol 8 397 403
5. NurnbergerT
BrunnerF
KemmerlingB
PiaterL
2004 Innate immunity in plants and animals: striking similarities and obvious differences. Immunol Rev 198 249 266
6. ZhangHJ
FangQ
ZhangZG
WangYC
ZhengXB
2009 The role of respiratory burst oxidase homologues in elicitor-induced stomatal closure and hypersensitive response in Nicotiana benthamiana. J Exp Bot 60 3109 3122
7. GanYZ
ZhangLS
ZhangZG
DongSM
LiJ
2009 The LCB2 subunit of the sphingolip biosynthesis enzyme serine palmitoyltransferase can function as an attenuator of the hypersensitive response and Bax-induced cell death. New Phytol 181 127 146
8. LambC
DixonRA
1997 The Oxidative Burst in Plant Disease Resistance. Annu Rev Plant Physiol Plant Mol Biol 48 251 275
9. MellershDG
FouldsIV
HigginsVJ
HeathMC
2002 H2O2 plays different roles in determining penetration failure in three diverse plant-fungal interactions. Plant J 29 257 268
10. CessnaSG
SearsVE
DickmanMB
LowPS
2000 Oxalic acid, a pathogenicity factor for Sclerotinia sclerotiorum, suppresses the oxidative burst of the host plant. Plant Cell 12 2191 2200
11. MayerAM
StaplesRC
Gil-adNL
2001 Mechanisms of survival of necrotrophic fungal plant pathogens in hosts expressing the hypersensitive response. Phytochemistry 58 33 41
12. Moye-RowleyWS
2003 Regulation of the transcriptional response to oxidative stress in fungi: similarities and differences. Eukaryot Cell 2 381 389
13. ApelK
HirtH
2004 Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 55 373 399
14. LinCH
YangSL
ChungKR
2009 The YAP1 homolog-mediated oxidative stress tolerance is crucial for pathogenicity of the necrotrophic fungus Alternaria alternata in citrus. Mol Plant Microbe Interact 22 942 952
15. MolinaL
KahmannR
2007 An Ustilago maydis gene involved in H2O2 detoxification is required for virulence. Plant Cell 19 2293 2309
16. GuoM
GuoW
ChenY
DongSM
ZhangX
2010 The basic leucine zipper transcription factor Moatf1 mediates oxidative stress responses and is necessary for full virulence of the rice blast fungus Magnaporthe oryzae. Mol Plant Microbe Interact 23 1053 1068
17. KawasakiL
WysongD
DiamondR
AguirreJ
1997 Two divergent catalase genes are differentially regulated during Aspergillus nidulans development and oxidative stress. J Bacteriol 179 3284 3292
18. LanfrancoL
NoveroM
BonfanteP
2005 The mycorrhizal fungus Gigaspora margarita possesses a CuZn superoxide dismutase that is up-regulated during symbiosis with legume hosts. Plant Physiol 137 1319 1330
19. NavarroRE
StringerMA
HansbergW
TimberlakeWE
AguirreJ
1996 catA, a new Aspergillus nidulans gene encoding a developmentally regulated catalase. Curr Genet 29 352 359
20. TooneWM
MorganBA
JonesN
2001 Redox control of AP-1-like factors in yeast and beyond. Oncogene 20 2336 2346
21. KugeS
JonesN
1994 YAP1 dependent activation of TRX2 is essential for the response of Saccharomyces cerevisiae to oxidative stress by hydroperoxides. EMBO J 13 655 664
22. SchnellN
KremsB
EntianKD
1992 The PAR1 (YAP1/SNQ3) gene of Saccharomyces cerevisiae, a c-jun homologue, is involved in oxygen metabolism. Curr Genet 21 269 273
23. GrantCM
CollinsonLP
RoeJH
DawesIW
1996 Yeast glutathione reductase is required for protection against oxidative stress and is a target gene for yAP-1 transcriptional regulation. Mol Microbiol 21 171 179
24. EllenbergerTE
BrandlCJ
StruhlK
HarrisonSC
1992 The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted alpha helices: crystal structure of the protein-DNA complex. Cell 71 1223 1237
25. O'SheaEK
KlemmJD
KimPS
AlberT
1991 X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. Science 254 539 544
26. DelaunayA
IsnardA-D
ToledanoMB
2000 H2O2 sensing through oxidation of the Yap1 transcription factor. EMBO J 19 5157 5166
27. ColemanST
EppingEA
SteggerdaSM
Moye-RowleyWS
1999 Yap1p activates gene transcription in an oxidant-specific fashion. Mol Cell Biol 19 8302 8313
28. KugeS
AritaM
MurayamaA
MaetaK
IzawaS
2001 Regulation of the yeast Yap1p nuclear export signal is mediated by redox signal-induced reversible disulfide bond formation. Mol Cell Biol 21 6139 6150
29. TooneWM
JonesN
1999 AP-1 transcription factors in yeast. Curr Opin Genet Dev 9 55 61
30. LevS
HadarR
AmedeoP
BakerSE
YoderOC
2005 Activation of an AP1-like transcription factor of the maize pathogen Cochliobolus heterostrophus in response to oxidative stress and plant signals. Eukaryot Cell 4 443 454
31. EnjalbertB
MacCallumDM
OddsFC
BrownAJ
2007 Niche-specific activation of the oxidative stress response by the pathogenic fungus Candida albicans. Infect Immun 75 2143 2151
32. LessingF
KniemeyerO
WozniokI
LoefflerJ
KurzaiO
2007 The Aspergillus fumigatus transcriptional regulator AfYap1 represents the major regulator for defense against reactive oxygen intermediates but is dispensable for pathogenicity in an intranasal mouse infection model. Eukaryot Cell 6 2290 2302
33. TalbotNJ
2003 On the trail of a cereal killer: Exploring the biology of Magnaporthe grisea. Annu Rev Microbiol 57 177 202
34. TalbotNJ
FosterAJ
2001 Genetics and genomics of the rice blast fungus Magnaporthe grisea: Developing an experimental model for understanding fungal diseases of cereals. Advances in Botanical Researc Academic Press 263 287
35. BourettTM
HowardRJ
1991 In vitro development of penetration structures in the rice blast fungus Magnaporthe grisea. Can J Bot 68 329 342
36. HowardRJ
FerrariMA
RoachDH
MoneyNP
1991 Penetration of hard substrates by a fungus employing enormous turgor pressures. Proc Natl Acad Sci U S A 88 11281 11284
37. KankanalaP
CzymmekK
ValentB
2007 Roles for rice membrane dynamics and plasmodesmata during biotrophic invasion by the blast fungus. Plant Cell 19 706 724
38. MosqueraG
GiraldoMC
KhangCH
CoughlanS
ValentB
2009 Interaction transcriptome analysis identifies Magnaporthe oryzae BAS1-4 as Biotrophy-associated secreted proteins in rice blast disease. Plant Cell 21 1273 1290
39. EbboleDJ
2007 Magnaporthe as a model for understanding host-pathogen interactions. Annu Rev Phytopathol 45 437 456
40. DeanRA
TalbotNJ
EbboleDJ
FarmanML
MitchellTK
2005 The genome sequence of the rice blast fungus Magnaporthe grisea. Nature 434 980 986
41. YanC
LeeLH
DavisLI
1998 Crm1p mediates regulated nuclear export of a yeast AP-1-like transcription factor. EMBO J 17 7416 7429
42. LeeK
SinghP
ChungWC
AshJ
KimTS
2006 Light regulation of asexual development in the rice blast fungus, Magnaporthe oryzae. Fungal Genet Biol 43 694 706
43. ZhangHF
ZhaoQ
LiuKY
ZhangZG
WangYC
2009 MgCRZ1, a transcription factor of Magnaporthe grisea, controls growth, development and is involved in full virulence. FEMS Microbiol Lett 293 160 169
44. NguyenAN
LeeA
PlaceW
ShiozakiK
2000 Multistep phosphorelay proteins transmit oxidative stress signals to the fission yeast stress-activated protein kinase. Mol Biol Cell 11 1169 1181
45. QuinnJ
FindlayVJ
DawsonK
MillarJB
JonesN
2002 Distinct regulatory proteins control the graded transcriptional response to increasing H2O2 levels in fission yeast Schizosaccharomyces pombe. Mol Biol Cell 13 805 816
46. EganMJ
WangZY
JonesMA
SmirnoffN
TalbotNJ
2007 Generation of reactive oxygen species by fungal NADPH oxidases is required for rice blast disease. Proc Natl Acad Sci U S A 104 11772 11777
47. XuJR
StaigerCJ
HamerJE
1998 Inactivation of the mitogen-activated protein kinase Mps1 from the rice blast fungus prevents penetration of host cells but allows activation of plant defense responses. Proc Natl Acad Sci U S A 95 12713 12718
48. XuJR
2000 Map kinases in fungal pathogens. Fungal Genet Biol 31 137 152
49. SkamniotiP
HendersonC
ZhangZ
RobinsonZ
GurrSJ
2007 A novel role for catalase B in the maintenance of fungal cell-wall integrity during host invasion in the rice blast fungus Magnaporthe grisea. Mol Plant Microbe Interact 20 568 580
50. JeonJ
GohJ
YooS
ChiMH
ChoiJ
2008 A putative MAP kinase kinase kinase, MCK1, is required for cell wall integrity and pathogenicity of the rice blast fungus, Magnaporthe oryzae. Mol Plant Microbe Interact 21 525 534
51. WoodPJ
FulcherRG
1983 Dye interactions. A basis for specific detection and histochemistry of polysaccharides. J Histochem Cytochem 31 823 826
52. GalhaupC
HaltrichD
2001 Enhanced formation of laccase activity by the white-rot fungus Trametes pubescens in the presence of copper. Appl Microbiol Biotechnol 56 225 232
53. ParisotD
DufresneM
VeneaultC
LaugeR
LanginT
2002 clap1, a gene encoding a copper-transporting ATPase involved in the process of infection by the phytopathogenic fungus Colletotrichum lindemuthianum. Mol Genet Genomics 268 139 151
54. ZhouZ
LiG
LinC
HeC
2009 Conidiophore stalk-less1 encodes a putative zinc-finger protein involved in the early stage of conidiation and mycelial infection in Magnaporthe oryzae. Mol Plant Microbe Interact 22 402 410
55. TuckerSL
BesiMI
GalhanoR
FranceschettiM
GoetzS
2010 Common genetic pathways regulate organ-specific infection-related development in the rice blast fungus. Plant Cell 22 953 972
56. SesmaA
OsbournAE
2004 The rice leaf blast pathogen undergoes developmental processes typical of root-infecting fungi. Nature 431 582 586
57. SiluD
TharreauD
TalbotNJ
ClergeotPH
NotteghemJL
1998 Identification and characterization of apf1-in a non-pathogenic mutant of the rice blast fungus Magnaporthe grisea which is unable to differentiate appressoria. Physiol Mol Plant Pathol 53 239 251
58. KimS
ParkSY
KimKS
RhoHS
ChiMH
2009 Homeobox transcription factors are required for conidiation and appressorium development in the rice blast fungus Magnaporthe oryzae. PLoS Genet 5 e1000757
59. AnderssonRA
KoivV
Norman-SetterbladC
PirhonenM
1999 Role of RpoS in virulence and stress tolerance of the plant pathogen Erwinia carotovora subsp. carotovora. Microbiology 145 (Pt 12) 3547 3556
60. ChiMH
ParkSY
KimS
LeeYH
2009 A novel pathogenicity gene is required in the rice blast fungus to suppress the basal defenses of the host. PLoS Pathog 5 e1000401
61. WoodMJ
AndradeEC
StorzG
2003 The redox domain of the Yap1p transcription factor contains two disulfide bonds. Biochemistry 42 11982 11991
62. AlarcoAM
RaymondM
1999 The bZip transcription factor Cap1p is involved in multidrug resistance and oxidative stress response in Candida albicans. J Bacteriol 181 700 708
63. BelozerskaiaTA
GesslerNN
2007 Reactive oxygen species and the strategy of the antioxidant defense in fungi: a review. Prikl Biokhim Mikrobiol 43 565 575
64. Del SorboG
SchoonbeekH
De WaardMA
2000 Fungal transporters involved in efflux of natural toxic compounds and fungicides. Fungal Genet Biol 30 1 15
65. OsbournAE
2001 Tox-boxes, fungal secondary metabolites, and plant disease. Proc Natl Acad Sci USA 98 14187 14188
66. Hammond-KosackKE
JonesJD
1996 Resistance gene-dependent plant defense responses. Plant Cell 8 1773 1791
67. D'AutreauxB
ToledanoMB
2007 ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8 813 824
68. MittlerR
2002 Oxidative stress, antioxidants and stress tolerance. Trends Plant Sci 7 405 410
69. AguirreJ
Rios-MombergM
HewittD
HansbergW
2005 Reactive oxygen species and development in microbial eukaryotes. Trends Microbiol 13 111 118
70. HuckelhovenR
KogelKH
2003 Reactive oxygen intermediates in plant-microbe interactions: who is who in powdery mildew resistance? Planta 216 891 902
71. ShettyNP
MehrabiR
LutkenH
HaldrupA
KemaGH
2007 Role of hydrogen peroxide during the interaction between the hemibiotrophic fungal pathogen Septoria tritici and wheat. New Phytol 174 637 647
72. TakemotoD
TanakaA
ScottB
2006 A p67Phox-like regulator is recruited to control hyphal branching in a fungal-grass mutualistic symbiosis. Plant Cell 18 2807 2821
73. TanakaA
ChristensenMJ
TakemotoD
ParkP
ScottB
2006 Reactive oxygen species play a role in regulating a fungus-perennial ryegrass mutualistic interaction. Plant Cell 18 1052 1066
74. TanakaA
TakemotoD
HyonGS
ParkP
ScottB
2008 NoxA activation by the small GTPase RacA is required to maintain a mutualistic symbiotic association between Epichloë festucae and perennial ryegrass. Mol Microbiol 68 1165 1178
75. GiesbertS
SchurgT
ScheeleS
TudzynskiP
2008 The NADPH oxidase Cpnox1 is required for full pathogenicity of the ergot fungus Claviceps purpurea. Mol Plant Pathol 9 317 327
76. SegmullerN
KokkelinkL
GiesbertS
OdiniusD
van KanJ
2008 NADPH oxidases are involved in differentiation and pathogenicity in Botrytis cinerea. Mol Plant Microbe Interact 21 808 819
77. KimKH
WillgerSD
ParkSW
PuttikamonkulS
GrahlN
2009 TmpL, a transmembrane protein required for intracellular redox homeostasis and virulence in a plant and an animal fungal pathogen. PLoS Pathog 5 e1000653
78. GesslerNN
Aver'yanovAA
BelozerskayaTA
2007 Reactive oxygen species in regulation of fungal development. Biochemistry (Mosc) 72 1091 1109
79. Bar-NunnN
Tal-LevA
HarelE
MayerAM
1988 Repression of laccase formation in Botrytis cinerea and its possible relation to phytopathogenicity. Phytochemistry 27 2505 2509
80. SkamniotiP
GurrSJ
2007 Magnaporthe grisea cutinase2 mediates appressorium differentiation and host penetration and is required for full virulence. Plant Cell 19 2674 2689
81. ZhengW
ChenJ
LiuW
ZhengS
ZhouJ
2007 A Rho3 homolog is essential for appressorium development and pathogenicity of Magnaporthe grisea. Eukaryot Cell 6 2240 2250
82. ZhaoX
KimY
ParkG
XuJR
2005 A mitogen-activated protein kinase cascade regulating infection-related morphogenesis in Magnaporthe grisea. Plant Cell 17 1317 1329
83. XuJR
HamerJE
1996 MAP kinase and cAMP signaling regulate infection structure formation and pathogenic growth in the rice blast fungus Magnaporthe grisea. Genes Dev 10 2696 2706
84. NishimuraM
ParkG
XuJR
2003 The G-beta subunit MGB1 is involved in regulating multiple steps of infection-related morphogenesis in Magnaporthe grisea. Mol Microbiol 50 231 243
85. TillakaratneNJ
Medina-KauweL
GibsonKM
1995 gamma-Aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues. Comp Biochem Physiol A Physiol 112 247 263
86. ColemanST
FangTK
RovinskySA
TuranoFJ
Moye-RowleyWS
2001 Expression of a glutamate decarboxylase homologue is required for normal oxidative stress tolerance in Saccharomyces cerevisiae. J Biol Chem 276 244 250
87. BoucheN
FaitA
BouchezD
MollerSG
FrommH
2003 Mitochondrial succinic-semialdehyde dehydrogenase of the gamma-aminobutyrate shunt is required to restrict levels of reactive oxygen intermediates in plants. Proc Natl Acad Sci U S A 100 6843 6848
88. ShelpBJ
BownAW
McLeanMD
1999 Metabolism and functions of gamma-aminobutyric acid. Trends Plant Sci 4 446 452
89. TalbotNJ
EbboleDJ
HamerJE
1993 Identification and characterization of MPG1, a gene involved in pathogenicity from the rice blast fungus Magnaporthe grisea. Plant Cell 5 1575 1590
90. CarrollA
SweigardJ
ValentB
1994 Improved vectors for selecting resistance to hygromycin. Fungal Genet Newsl 41 22
91. SambrookJ
FritschEF
ManiatisT
1989 Molecular Cloning: a Laboratory Manual. Cold Spring Harbor, NY Cold Spring Harbor Laboratory Press
92. ChenJ
ZhengW
ZhengS
ZhangD
SangW
2008 Rac1 is required for pathogenicity and Chm1-dependent conidiogenesis in rice fungal pathogen Magnaporthe grisea. PLoS Pathog 4 e1000202
93. HarrisSD
MorrellJL
HamerJE
1994 Identification and characterization of Aspergillus nidulans mutants defective in cytokinesis. Genetics 136 517 532
94. McGinnisS
MaddenTL
2004 BLAST: at the core of a powerful and diverse set of sequence analysis tools. Nucleic Acids Res 32 W20 25
95. ThompsonJD
HigginsDG
GibsonTJ
1994 CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22 4673 4680
96. KumarS
TamuraK
NeiM
2004 MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinform 5 150 163
97. AshburnerM
BallCA
BlakeJA
BotsteinD
ButlerH
2000 Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25 25 29
98. BendtsenJD
NielsenH
von HeijneG
BrunakS
2004 Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340 783 795
99. ZhuC
ByersKJ
McCordRP
ShiZ
BergerMF
2009 High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19 556 566
100. HarbisonCT
GordonDB
LeeTI
RinaldiNJ
MacisaacKD
2004 Transcriptional regulatory code of a eukaryotic genome. Nature 431 99 104
101. NguyenDT
AlarcoAM
RaymondM
2001 Multiple Yap1p-binding sites mediate induction of the yeast major facilitator FLR1 gene in response to drugs, oxidants, and alkylating agents. J Biol Chem 276 1138 1145
102. BalhadèrePV
TalbotNJ
2001 PDE1 Encodes a P-Type ATPase Involved in Appressorium-Mediated Plant Infection by the Rice Blast Fungus Magnaporthe grisea. Plant Cell 13 1987 2004
103. JeongJS
MitchellTK
DeanRA
2007 The Magnaporthe grisea snodprot1 homolog, MSP1, is required for virulence. FEMS Microbiol Lett 273 157 65
104. ChoiW
DeanRA
1997 The adenylate cyclase gene MAC1 of Magnaporthe grisea controls appressorium formation and other aspects of growth and development. Plant Cell 9 1973 83
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