endocycling in the path of plant development

Endocycling in the path of plant developmentChristian Breuer1, Luke Braidwood1 and Keiko Sugimoto

Available online at www.sciencedirect.com

ScienceDirect

Genome duplication is a widespread phenomenon in many

eukaryotes. In plants numeric changes of chromosome sets

have tremendous impact on growth performance and yields,

hence, are of high importance for agriculture. In contrast to

polyploidisation in which the genome is duplicated throughout

the entire organism and stably inherited by the offspring,

endopolyploidy relies on endocycles in which cells multiply the

genome in specific tissues and cell types. During the endocycle

cells repeatedly replicate their DNA but skip mitosis, leading to

genome duplication after each round. Endocycles are common

in multicellular eukaryotes and are often involved in the

regulation of cell and organ growth. In plants, changes in

cellular ploidy have also been associated with other

developmental processes as well as physiological interactions

with the surrounding environment. Thus, endocycles play

pivotal roles throughout the life cycle of many plant species.

Addresses

RIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho,

Tsurumi, Yokohama, Kanagawa 230-0045, Japan

Corresponding authors: Sugimoto, Keiko ([email protected],

[email protected])

1 These authors contributed equally to this work and should be

considered joint first authors.

Current Opinion in Plant Biology 2014, 17:78–85

This review comes from a themed issue on Growth and development

Edited by David R Smyth and Jo Ann Banks

1369-5266/$ – see front matter, Published by Elsevier Ltd.

http://dx.doi.org/10.1016/j.pbi.2013.11.007

IntroductionOrderly progression through the four phases of the mitotic

cell cycle (G1, S, G2 and M phase) is essential for genome

replication and the subsequent separation of chromo-

somes into two daughter cells. In multicellular plants,

meristems serve as the main sites for cell production, so

determine the final number of cells within their respect-

ive organs. As cells exit the mitotic programme and leave

meristematic regions in roots, shoots and leaf primordia,

they start to undergo cell differentiation. During this

process cells often continue DNA replication but omit

cell divisions; they are increasing cellular ploidy through

the endocycle. The molecular impacts of endocycle-dri-

ven endopolyploidisation are still elusive but various

studies have illustrated that ploidy often positively cor-

relates with the extent of post-mitotic cell growth and


expansion [1]. Studies during the past decade, in addition,

have revealed that endoreduplication also plays central

roles for other developmental processes including the

maintenance of cellular specification, cell morphogenesis

and as well as physiological processes such as plant–pathogen interactions and adaptive plant growth under

harsh environments [2,3].

Endocycles are widespread in animals and plants, and are

also reported in bacteria [4]. Most angiosperms and

mosses perform endocycles in specialised cells or tissues,

but endocycling appears to be absent in liverworts, club-

mosses, ferns, and gymnosperms [5,6]. This scattered

distribution suggests that endoreduplication has evolved

multiple times during evolution and that endocycling is

not detrimental to plant fitness, but likely increases it in

appropriate contexts. Endocycles occur predominantly in

cells with large volumes, and in cells with high metabolic

activity, implying that increased ploidy elevates global

gene expression and macromolecular production to meet

high energy demands. For the past decade, Arabidopsis

leaf hairs (trichomes) have served as a prominent single

cell system to study the impact of endocycles on cell

growth and morphogenesis. Trichomes are one of the

largest cell types in Arabidopsis, consisting of a stalk,

usually with three branches. Generally, trichome mutants

with increased endoreduplication over-branch, whereas a

decrease in trichome endoreduplication results in

reduction of trichome branch numbers. Examples that

do not follow this positive correlation are known but rare

[7]. Endoreduplication is also important for tissue de-

velopment in several plant species of agro-economic in-

terest such as the cereal endosperm, tomato fruits and

cotton fibres [8–10]. This review will discuss recent

findings for the molecular regulation of endocycle onset,

progression and termination during plant development.

The road to polyploidy: short-cuts off themitotic cell cycleIn principle, an endoreduplication cycle includes a com-

plete genome replication (S phase) but lacks all M phase-

specific features such as chromosomal separation and cell

division (Figure 1) [11,12]. In nature, however, several

variants of this process have been discovered, such as

when re-replication is incomplete or only occurs in

particular chromosomal hotspots [13,14]. Another cell

cycle variant leading to increased cellular ploidy is endo-

mitosis. In contrast to the endocycle, cells undergoing

endomitosis exhibit partial mitotic characteristics, such as

the separation of sister-chromatids, but skip cell division

(Figure 1).

www.sciencedirect.com

[email protected]

[email protected]

http://dx.doi.org/10.1016/j.pbi.2013.11.007

http://www.sciencedirect.com/science/journal/13695266

Endocycle regulation in plant development Breuer, Braidwood and Sugimoto 79

Figure 1

Mitotic cell cycle Endocycle Endomitosis Partial endocycleM G G

G2 G1

M

SSSS

2N/2C 2N/2C 2N/2C 2N/2C

2N/2+XC4N/4C2N/4C2N/2C2N/2C

G1G2

Current Opinion in Plant Biology

Endocycles in plants. Deviation from the mitotic cell cycle results in endopolyploid cells during vegetative plant development. Endocycling cells

duplicate their DNA content (C) and form polytene chromosomes. In contrast, endomitosis leads to a separation of sister-chromatids and cells double

their chromosome number (4N/4C). Cells undergoing partial endocycles skip M phase and re-replicate only specific chromosomal regions. Those cells

are diploid but their total increase in DNA content is only partial (2N/2 + XC).

The plant endocycle machinery — onset,progression and exitAs an alternative mode of cell cycle, it is not surprising

that the endocycle utilises many elements of the mitotic

cycle, including cyclins (CYC), cyclin-dependent kinases

(CDKs) and CDK inhibitors. Recent evidence suggests

that in addition, the onset, progression and exit of the

endocycle are fine-tuned by additional regulators that

modulate transcription and/or post-translational modifi-

cation of these core cell cycle regulators.

Getting into the endocycle

In order to exit the mitotic programme and transit into the

endocycle, the activity of certain CYC–CDK complexes

must be down-regulated. This general principle is con-

served amongst eukaryotes [2,12]. CYC–CDK activity is

reduced by several mechanisms including transcriptional

regulation, proteolysis and interactions with CDK inhibi-

tors. Recent findings are described in detail below and

summarised for Arabidopsis trichomes and roots in

Figure 2.

Degradation of CYCs is one key trigger of endocycle

entry and an E3-ubiquitin ligase complex, the anaphase-

promoting complex/cyclosome (APC/C) plays a central

role in this process. The APC/C is a multimeric protein

complex comprising 11 core subunits regulated by several

activators and inhibitors [15,16]. Prominent classes of


APC/C activators are CELL CYCLE SWITCH 52

(CCS52) and CELL DIVISION CYCLE 20 (CDC20)

proteins, which have homologs in animals and yeast.

CCS52 proteins generally block the mitotic programme

and induce endocycle onset in plants [17–22]. For

instance, Arabidopsis ccs52a1 mutants exhibit delayed

endocycle entry in roots caused by a decrease in APC/

C activity and thus stabilisation of CYCA2;3 proteins [23].

SAMBA, another plant-specific APC/C activator, was

recently identified as a negative regulator of cell division

during embryogenesis and early seedling development.

SAMBA physically interacts with A-type CYCs and pro-

motes their degradation since CYCA2;3 levels are elev-

ated in samba mutants [24]. Despite the increase in cell

division through stabilisation of CYCA2;3, endocycle

onset is not affected in samba leaves. Surprisingly, endor-

eduplication levels in samba are higher compared to wild

type, promoting further cell growth, however, this might

be caused by mis-regulation of other cell cycle genes [24].

Recent studies have also uncovered plant-specific inhibi-

tors of the APC/C. ULTRAVIOLET-B-INSENSITIVE

4 (UVI4) negatively controls the APC/C by inhibiting

CCS52A1 through direct interaction [25�,26�]. Accord-

ingly, loss of UVI4 leads to hyper-activation of the APC/

CCCS52A1 and increased degradation of CYCA2;3. As a

consequence, uvi4 mutants have larger, over-branched

trichomes with higher ploidy as well as reduced root

meristem size and reduced cell number in leaves. The


80 Growth and development

Arabidopsis genome also encodes a UVI4 homolog,

OMISSION OF SECOND DIVISION 1 (OSD1)/

GIGAS CELL 1 (GIG1), initially identified as a regulator

for the second mitotic division during meiosis [27]. Iwata

et al. subsequently discovered that guard cells in osd1/gig1undergo endomitosis, leading to higher ploidy and

dramatically increased cell size [26�]. OSD1/GIG1

appears to prevent endomitosis in guard cells through

the interaction with CCS52 and CDC20 proteins, causing

stabilisation of mitotic B-type CYCs.

A group of plant-specific CDK inhibitors that belong to

the SIAMESE (SIM) and SIAMESE-RELATED

(SMR) family also function in the mitotic-to-endocycle

transition. Mutation of SIM causes multicellular tri-

chomes and its overexpression enhances endocycling,

hence SIM blocks cell division and promotes endo-

cycles in trichomes. SIM interacts with CYCD3 and

CDKA;1, suggesting that SIM regulates the activity of

these CYCD3–CDKA complexes [28]. This is consist-

ent with other studies showing the repression of the

mitotic cycle and promotion of endocycles in cycd3triple mutants while CYCD3 overexpression results

in multicellular trichomes [29,30]. SMR1/LOSS OF

GIANT CELLS FROM ORGANS (LGO) also posi-

tively regulates endoreduplication in sepals and leaves,

suggesting a conserved function of this gene family in

endocycle onset [31].

The transition into the endocycle is also regulated by E2F

transcription factors. For instance, the atypical E2F tran-

scription factor DEL1 directly represses CCS52A2 expres-

sion in both roots and shoots [19]. Ectopic expression of

DEL1 delays the mitotic exit whereas loss of DEL1accelerates the mitotic-to-endocycle transition [19,32].

Furthermore, E2Fa-RETINOBLASTOMA-RELATED

(RBR) represses the expression of CCS52A1 and CCS52A2in meristems to prevent endocycle entry [33��]. Tran-

scriptional control of APC/C activators by E2F transcrip-

tion factors at the mitotic-to-endocycle-transition appears

to be conserved in eukaryotes since similar mechanisms

are also described in animals [34].

Progression and termination of the endocycle

How plant cells successively replicate DNA and even-

tually cease endocycling is far less understood. In endor-

eduplicating animal cells CYCE–CDK complexes exhibit

oscillating abundances and thus cyclic activities [34]. It is

very likely that plants also possess oscillating CYC–CDK

activities to control initiation of replication but also to

allow gap phases to ensure completion of S phase and

DNA integrity before re-entering S phase (Figure 3)

[1,12]. A recent study by Roodbarkelari et al. puts forward

an attractive two-step model for endocycle progression in

trichome cells [35�]. While endocycle onset in trichomes

relies on the combined action of SIM and APC/CCCS52A1

[36], its progression is regulated by cyclic degradation of


the Kip-related protein (KRP) class of CDK inhibitors by

the Cullin-RING ubiquitin ligase (CRL). By doing so, the

cyclic activities of the CRL are thought to generate

oscillating levels of S phase-specific CDK activities

[35�]. Expanding this concept into other cell types will

be a major challenge in future studies and overcoming

functional redundancies amongst SMRs and KRPs will be

essential to undertake these tasks.

A recent study on Arabidopsis trichomes provided new

insights into how plants control the endocycle cessation

at transcriptional level. The trihelix transcription factor

GT-2-LIKE 1 (GTL1) actively terminates endocycle

progression by directly repressing CCS52A1 expression

during the late stage of trichome development

(Figure 2a) [37,38��]. Repression of CCS52A1 expres-

sion might lead to a transient stabilisation of active

CYC–CDK, thus causing termination of the endocycle.

This view is supported by another study which demon-

strated that, for instance, CYCA2;3 is crucial for endo-

cycle termination in trichomes [39]. Put together, it

appears that endocycle onset and cessation are mainly

controlled by the presence and absence of APC/

CCCS52A1, respectively, whereas progression through

the successive rounds of endocycles is regulated

by CRL-type RING ubiquitin ligases (Figures 2 and 3).

Developmental and environmental impacts onendocycles and cell differentiationDynamic growth and development of plants are the

results of continuous interactions between endogenous

developmental programmes and exogenous environmen-

tal cues [40]. Recent studies are starting to unveil how

those interactions affect the endocycle and thereby alter

cell fate and differentiation.

Endocycle onset and progression in trichomes depends

on developmental programmes that pattern or specify

trichome fate but also require structural components

such as the DNA topoisomerase VI complex [41,42].

During trichome initiation, the GLABRA 1 (GL1)–GL3

transcription factor complex synchronises endocycle

onset and differentiation through simultaneous induc-

tion of SIM and the growth-promoting homeodomain

transcription factor GLABRA 2 (GL2) (Figure 2a) [43].

GL2 and GL3 also seem to have cooperative roles for

endocycle promotion since the reduced ploidy pheno-

type in their single mutants is enhanced in gl2 gl3double mutants. The gl2 gl3 mutants completely abol-

ish trichome endoreduplication, leading to a loss of

trichome cell fate [44�]. In addition, a recent study

identified BRANCHLESS TRICHOMES (BLT) as a

positive regulator of trichome branching and endore-

duplication [45]. Unlike the early patterning genes,

BLT does not interfere with the endocycle initiation

and promotes only its progression through a yet

unknown mechanism.



Figure 2

(a)

(b)

Cell fate/initiation

Cell division Endocycles

CYC

CDK

CYC

CDK

CYC

CDK

SIM KRP

CRL

GL2

GL1GL3

CYCA2;3

CDKB1;1

APC/C

CCS52A1RBR

UV14

ARR2E2Fa

AUXIN CYTOKININ

CYTOKININ

? ?APC/C APC/C

CCS52A1

GTL1BLT

UV14

CCS52A1

Root meristem

Cell division

Transitionzone

Endocycles

Elongation and differentiation zone

Exit Entry Progression Exit

Exit Entry

Outgrowth Branching Cell growth andexpansion

Maturation


Control of endocycles in Arabidopsis trichomes and root tips. (a) In trichomes, mitotic-to-endocycle transition is developmentally regulated by the

GL1–GL3 transcription factor complex which acts through SIM. The APC/CCCS52A1 complex also performs cooperative roles at the transition.

Progression through alternating S and G phases seems to be under control of the CRL complex by generating oscillations in KRP levels and CYC–CDK

activities. The endocycle exit is transcriptionally regulated by the trihelix transcription factor GTL1 during late trichome development. The

developmental factors GL2 and BLT also contribute to the progression of endocycles and cell morphogenesis in trichomes but their exact roles in cell

and endocycle regulation is elusive. (b) The antagonising action of auxin and cytokinin developmentally determine meristem size and onset of cell

www.sciencedirect.com Current Opinion in Plant Biology 2014, 17:78–85


Figure 3

Activity

CDKs?

?

?

8C4C2C4C

Mitotic Cell Cycle Endocycle Cell Cycle Arrest

M

S S

2CG1

G1

G2

GE G0

G2 GE GE G0M S SS

CDK-Degrading Ub Ligases(APC/C, CRL4)


Model for cell cycle and endocycle regulation by opposing activities of ubiquitin ligase- and CDK-complex. The activity of CYC–CDK complexes is

counteracted by the ubiquitin ligases APC/C and CRL4. The repression of M phase-specific of CDK activities is critical to trigger endocycle onset and

to avoid mitotic processes during endocycle progression. Oscillating activities are essential to establish alternating endocycle-specific G (GE) and S

phases. During termination of the endocycle, APC/C activities cease and thus keep the cell in a stable G0 state. At this stage, abundance and activity of

CDK complexes remain unclear but might eventually drop (grey lines).

The endocycle is also connected with developmental

programmes underlying organogenesis. In Arabidopsis

roots, for example, the antagonistic action of auxin and

cytokinin has been linked to the mitotic-to-endocycle

transition since auxin inhibits endocycle onset whereas

cytokinin promotes it (Figure 2b) [46]. As cells switch into

the endocycle, they concomitantly undergo rapid increase

in cell size, which is developmentally controlled by key

regulators of cytokinin signalling, B-type ARABIDOPSIS

RESPONSE REGULATORs (ARRs), ARR1 and

ARR12 [47,48]. Interestingly, a recent study has revealed

that another B-type ARR transcription factor ARR2 acts

as a transcriptional activator of CCS52A1 in the root

meristem to trigger mitotic exit and establish endocycle

entry. Thus, cytokinin signalling appears to synchronise

endocycle entry and cell differentiation via combined

actions of several B-type ARRs [47,48,49��] (Figure 2b).

(Figure Legend Continued) elongation and differentiation in the root transiti

into the endocycle programme. Cytokinin signalling induces the mitotic-to-en

induces expression of the APC/C activator CCS52A1. Thus, cytokinin facilit

counteracted by RBR-bound E2F complexes. For full names of proteins, se


The gibberellic acid (GA)–DELLA pathway also regulates

initiation of endocycling and differentiation [50,51]. GA

promotes both cell proliferation and post-mitotic cell

growth through the proteolysis of DELLA proteins [51–55]. The GA–DELLA pathway plays predominant roles

for the integration of various environmental inputs into

developmental growth responses. For example, abiotic

stresses such as cold, salt and osmotic stress result in a

decrease of active GAs, which in turn stabilises DELLA

proteins to repress cell division and post-mitotic cell

growth [56,57]. This adaptive growth response allows

plants to keep their body size small during harsh environ-

mental conditions. A likely molecular mechanism that

triggers the stress-induced mitotic exit via DELLA signal-

ling has recently been suggested for Arabidopsis leaves.

Osmotic stress stabilises DELLA proteins, which impair

the expression of the APC/C inhibitor UVI4 and the

on zone. Concomitantly with the onset of cell differentiation, cells transit

docycle switch via the transcription factor ARR2, which transcriptionally

ates the synchronisation of both processes. The action of ARR2 is

e main text.



atypical E2F transcription factor DEL1. The decrease in

UVI4 and DEL1 expression leads to elevated APC/C

activities, which then forces an early mitotic-to-endocycle

transition [50]. UV-B irradiation is another environmental

factor that regulates DEL1 expression. Upon exposure to

UV-B, DEL1 expression drops, allowing expression of the

APC/C activator CCS52A2. This provokes an early mitotic-

to-endocycle transition, resulting in a reduction of cell

numbers in leaves. Moreover, longer UV-B exposure

elevates CCS52A2 expression, triggering extra endocycles

and causing increase in cell size. The increase in post-

mitotic cell growth might represent a mechanism that

compensates for reduced cell division in UV-B irradiated

leaves [58].

Light also affects DEL1 expression and a recent study

shows that under light DEL1 expression is transcription-

ally activated by the E2F transcription factor E2Fb to

maintain cell proliferation and repress endoreduplication

[59]. In contrast, extended dark period leads to the

proteolytic degradation of E2Fb, allowing the binding

of the competing E2Fc to the same cis element of the

DEL1 promoter. E2Fc is a transcriptional repressor and

inhibits DEL1 expression, promoting endocycles and cell

elongation particularly in hypocotyls.

Endocycles are also induced by biotic stimuli and they

play pivotal roles during the interaction between plants

and microorganisms, ranging from symbiotic rhizobia to

parasitic root nematodes. Recent studies illustrate that

APC/C activators, their transcriptional repressors and

KRPs are central to establish symbiosis and parasitism

[18,60,61].

ConclusionsDespite several important breakthroughs in recent years,

our knowledge on endocycle regulation is still rudimen-

tary and often limited to specific cell types. It is clear that

post-translational regulation of CYC–CDK complexes by

the APC/C and CRL ligases is pivotal for endocycle onset,

progression and cessation. It will be a future challenge to

visualise temporal protein abundances and CDK activi-

ties in vivo to improve the existing models. Furthermore,

it will be interesting to test those models in other cell

types that undergo endocycles such as vasculature and

root hairs. Many key regulatory proteins such as KRPs (7

members in Arabidopsis), SMRs (at least 4 members) and

CYCs (30 members), are encoded by highly redundant

gene families, thus it will be essential to take account of

their functional redundancies to elucidate their exact

roles in the cell cycle and other associated developmental

processes. As an alternative approach to assigning novel

gene functions, a combination of linkage and association

mapping recently revealed CYCD5;1 as a quantitative trait

gene influencing endoreduplication [62�]. In contrast to

other D-type CYCs, CYCD5;1 promotes endoreduplica-

tion. The opposing function of CYCD5;1 amongst D-type


CYCs suggest the existence of other inhibitory CYCs in

plants. That several B-type ARRs coordinate both the

mitotic-to-endocycle transition and the proliferation-to-

differentiation transition highlights the close relationship

between cell cycle and development [49��]. It will be

interesting to explore whether similar mechanisms also

synchronise the progression and/or termination of endo-

cycling and cell differentiation.

AcknowledgementsWe thank all members of the Sugimoto Laboratory for helpful discussions.This work was supported by grants from the Ministry of Education, Culture,Sports, Science and Technology (Grant Number 25840112 to CB, and22119010 and 23370026 to KS).

References and recommended readingPapers of particular interest, published within the period of review,have been highlighted as:

� of special interest�� of outstanding interest

1. Breuer C, Ishida T, Sugimoto K: Developmental control ofendocycles and cell growth in plants. Curr Opin Plant Biol 2010,13:654-660.

2. De Veylder L, Larkin JC, Schnittger A: Molecular control andfunction of endoreplication in development and physiology.Trends Plant Sci 2011, 16:624-634.

3. Rymen B, Sugimoto K: Tuning growth to the environmentaldemands. Curr Opin Plant Biol 2012, 15:683-690.

4. Mendell JE, Clements KD, Choat JH, Angert ER: Extremepolyploidy in a large bacterium. Proc Natl Acad Sci U S A 2008,105:6730-6734.

5. Bainard JD, Bainard LD, Henry TA, Fazekas AJ, Newmaster SG: Amultivariate analysis of variation in genome size andendoreduplication in angiosperms reveals strongphylogenetic signal and association with phenotypic traits.New Phytol 2012, 196:1240-1250.

6. Bainard JD, Forrest LL, Goffinet B, Newmaster SG: Nuclear DNAcontent variation and evolution in liverworts. Mol PhylogenetEvol 2013, 68:619-627.

7. Hulskamp M: Plant trichomes: a model for cell differentiation.Nat Rev Mol Cell Biol 2004, 5:471-480.

8. Chevalier C, Nafati M, Mathieu-Rivet E, Bourdon M, Frangne N,Cheniclet C, Renaudin JP, Gevaudant F, Hernould M: Elucidatingthe functional role of endoreduplication in tomato fruitdevelopment. Ann Bot 2011, 107:1159-1169.

9. Sabelli PA, Larkins BA: The contribution of cell cycle regulation toendosperm development. Sex Plant Reprod 2009, 22:207-219.

10. Wilkins TA, Rajasekaran K, Anderson DM: Cotton biotechnology.Crit Rev Plant Sci 2000, 19:511-550.

11. Bourdon M, Coriton O, Pirrello J, Cheniclet C, Brown SC, Poujol C,Chevalier C, Renaudin J-P, Frangne N: In planta quantification ofendoreduplication using fluorescent in situ hybridization(FISH). Plant J 2012, 66:1089-1099.

12. Fox DT, Duronio RJ: Endoreplication and polyploidy: insightsinto development and disease. Development 2013, 140:3-12.

13. Lepers-Andrzejewski S, Siljak-Yakovlev S, Brown SC, Wong M,Dron M: Diversity and dynamics of plant genome size: anexample of polysomaty from a cytogenetic study of Tahitianvanilla (Vanilla xtahitensis Orchidaceae). Am J Bot 2011,98:986-997.

14. Lima-de-Faria A, Pero R, Avanzi S, Durante M, Stahle U,D’Amato F, Granstrom H: Relation between ribosomal RNAgenes and the DNA satellites of Phaseolus coccineus.Hereditas 1975, 79:5-20.


http://refhub.elsevier.com/S1369-5266(13)00180-5/sbref0005













































15. Heyman J, De Veylder L: The anaphase-promoting complex/cyclosome in control of plant development. Mol Plant 2012,5:1182-1194.

16. Komaki S, Sugimoto K: Control of the plant cell cycle bydevelopmental and environmental cues. Plant Cell Physiol 2012,53:953-964.

17. Baloban M, Vanstraelen M, Tarayre S, Reuzeau C, Cultrone A,Mergaert P, Kondorosi E: Complementary and dose-dependentaction of AtCCS52A isoforms in endoreduplication and plantsize control. New Phytol 2013, 198:1049-1059.

18. Cebolla A, Vinardell JM, Kiss E, Olah B, Roudier F, Kondorosi A,Kondorosi E: The mitotic inhibitor ccs52 is required forendoreduplication and ploidy-dependent cell enlargement inplants. EMBO J 1999, 18:4476-4484.

19. Lammens T, Boudolf V, Kheibarshekan L, Zalmas LP,Gaamouche T, Maes S, Vanstraelen M, Kondorosi E, LaThangue NB, Govaerts W et al.: Atypical E2F activity restrainsAPC/CCCS52A2 function obligatory for endocycle onset. ProcNatl Acad Sci U S A 2008, 105:14721-14726.

20. Larson-Rabin Z, Li Z, Masson PH, Day CD: FZR2/CCS52A1expression is a determinant of endoreduplication and cellexpansion in Arabidopsis. Plant Physiol 2009, 149:874-884.

21. Tarayre S, Vinardell JM, Cebolla A, Kondorosi A, Kondorosi E: Twoclasses of the CDh1-type activators of the anaphase-promoting complex in plants: novel functional domains anddistinct regulation. Plant Cell 2004, 16:422-434.

22. Vanstraelen M, Baloban M, Da Ines O, Cultrone A, Lammens T,Boudolf V, Brown SC, De Veylder L, Mergaert P, Kondorosi E:APC/CCCS52A complexes control meristem maintenance inthe Arabidopsis root. Proc Natl Acad Sci 2009, 106:11806-11811.

23. Boudolf V, Lammens T, Boruc J, Van Leene J, Van Den Daele H,Maes S, Van Isterdael G, Russinova E, Kondorosi E, Witters E et al.:CDKB1;1 forms a functional complex with CYCA2;3 tosuppress endocycle onset. Plant Physiol 2009, 150:1482-1493.

24. Eloy NB, Gonzalez N, Van Leene J, Maleux K, Vanhaeren H, DeMilde L, Dhondt S, Vercruysse L, Witters E, Mercier R et al.:SAMBA, a plant-specific anaphase-promoting complex/cyclosome regulator is involved in early development and A-type cyclin stabilization. Proc Natl Acad Sci U S A 2012,109:13853-13858.

25.�

Heyman J, Van den Daele H, De Wit K, Boudolf V, Berckmans B,Verkest A, Alvim Kamei CL, De Jaeger G, Koncz C, De Veylder L:Arabidopsis ULTRAVIOLET-B-INSENSITIVE4 maintains celldivision activity by temporal inhibition of the anaphase-promoting complex/cyclosome. Plant Cell 2011, 23:4394-4410.

In this study and the study of the following reference the first negativeregulator of the APC/C is described in plants. UVI4 inhibits the activity ofthe APC/C through physical interaction with the APC/C activator CCS52.Similar mechanisms exist in animals although the lack of amino acidhomologies suggests that APC/C inhibitors evolved separately in botheukaryotic kingdoms.

26.�

Iwata E, Ikeda S, Matsunaga S, Kurata M, Yoshioka Y, Criqui MC,Genschik P, Ito M: GIGAS CELL1, a novel negative regulator ofthe anaphase-promoting complex/cyclosome, is required forproper mitotic progression and cell fate determination inArabidopsis. Plant Cell 2011, 23:4382-4393.

See annotation to Ref. [25�].

27. d’Erfurth I, Cromer L, Jolivet S, Girard C, Horlow C, Sun Y, To JP,Berchowitz LE, Copenhaver GP, Mercier R: The cyclin-ACYCA1;2/TAM is required for the meiosis I to meiosis IItransition and cooperates with OSD1 for the prophase to firstmeiotic division transition. PLoS Genet 2010, 6:e1000989.

28. Churchman ML, Brown ML, Kato N, Kirik V, Hulskamp M, Inze D, DeVeylder L, Walker JD, Zheng Z, Oppenheimer DG et al.: SIAMESE, aplant-specific cell cycle regulator, controls endoreplicationonset in Arabidopsis thaliana. Plant Cell 2006, 18:3145-3157.

29. Dewitte W, Scofield S, Alcasabas AA, Maughan SC, Menges M,Braun N, Collins C, Nieuwland J, Prinsen E, Sundaresan V et al.:Arabidopsis CYCD3 D-type cyclins link cell proliferation andendocycles and are rate-limiting for cytokinin responses. ProcNatl Acad Sci U S A 2007, 104:14537-14542.


30. Schnittger A, Schobinger U, Bouyer D, Weinl C, Stierhof YD,Hulskamp M: Ectopic D-type cyclin expression induces notonly DNA replication but also cell division in Arabidopsistrichomes. Proc Natl Acad Sci U S A 2002, 99:6410-6415.

31. Roeder AH, Chickarmane V, Cunha A, Obara B, Manjunath BS,Meyerowitz EM: Variability in the control of cell divisionunderlies sepal epidermal patterning in Arabidopsis thaliana.PLoS Biol 2010, 8:e1000367.

32. Vlieghe K, Boudolf V, Beemster GT, Maes S, Magyar Z,Atanassova A, de Almeida Engler J, De Groodt R, Inze D, DeVeylder L: The DP-E2F-like gene DEL1 controls the endocyclein Arabidopsis thaliana. Curr Biol 2005, 15:59-63.

33.��

Magyar Z, Horvath B, Khan S, Mohammed B, Henriques R, DeVeylder L, Bako L, Scheres B, Bogre L: Arabidopsis E2FAstimulates proliferation and endocycle separately throughRBR-bound and RBR-free complexes. EMBO J 2012,31:1480-1493.

This paper describes how RBR-bound and unbound E2F transcriptionalcomplexes regulate cell proliferation and endoreduplication in Arabidop-sis roots and leaves. The work suggests a molecular mechanism via theCCS52 class APC/C activators which balance cell proliferation activitiesin meristems and ploidy-dependent cell growth in differentiating tissues.

34. Lee HO, Davidson JM, Duronio RJ: Endoreplication: polyploidywith purpose. Genes Dev 2009, 23:2461-2477.

35.�

Roodbarkelari F, Bramsiepe J, Weinl C, Marquardt S, Novak B,Jakoby MJ, Lechner E, Genschik P, Schnittger A: Cullin 4-ringfinger-ligase plays a key role in the control of endoreplicationcycles in Arabidopsis trichomes. Proc Natl Acad Sci U S A 2010,107:15275-15280.

The authors use a trichome-specific RNAi approach that targets APC/Cand CRL components and illustrate that endocycle progression mainlydepends on CRL. The Cullin4-CRL ligase targets KRP for proteolysis, andthus, generating oscillations in the downstream activities of CYC–CDKcomplexes.

36. Kasili R, Walker JD, Simmons LA, Zhou J, De Veylder L, Larkin JC:SIAMESE cooperates with the CDH1-like protein CCS52A1 toestablish endoreplication in Arabidopsis thaliana trichomes.Genetics 2010, 185:257-268.

37. Breuer C, Kawamura A, Ichikawa T, Tominaga-Wada R, Wada T,Kondou Y, Muto S, Matsui M, Sugimoto K: The trihelix transcriptionfactor GTL1 regulates ploidy-dependent cell growth in theArabidopsis trichome. Plant Cell 2009, 21:2307-2322.

38.��

Breuer C, Morohashi K, Kawamura A, Takahashi N, Ishida T,Umeda M, Grotewold E, Sugimoto K: Transcriptional repressionof the APC/C activator CCS52A1 promotes active terminationof cell growth. EMBO J 2012, 31:4488-4501.

In this paper the authors identify the APC/C activator CCS52A1 as atranscriptional target of the growth repressing transcription factor GTL1.This study represents the first transcriptional mechanism in eukaryotesthat actively triggers cell growth cessation during terminal stages of celldifferentiation.

39. Imai KK, Ohashi Y, Tsuge T, Yoshizumi T, Matsui M, Oka A, Aoyama T:The A-type cyclin CYCA2;3 is a key regulator of ploidy levels inArabidopsis endoreduplication. Plant Cell 2006, 18:382-396.

40. Braidwood L, Breuer C, Sugimoto K: My body is a cage:mechanisms and modulation of plant cell growth. NewPhytologist 2014 http://dx.doi.org/10.1111/nph.12473.

41. Breuer C, Stacey NJ, West CE, Zhao Y, Chory J, Tsukaya H,Azumi Y, Maxwell A, Roberts K, Sugimoto-Shirasu K: BIN4, anovel component of the plant DNA topoisomerase VI complex,is required for endoreduplication in Arabidopsis. Plant Cell2007, 19:3655-3668.

42. Kirik V, Schrader A, Uhrig JF, Hulskamp M: MIDGET unravelsfunctions of the Arabidopsis topoisomerase VI complex inDNA endoreduplication, chromatin condensation, andtranscriptional silencing. Plant Cell 2007, 19:3100-3110.

43. Morohashi K, Grotewold E: A systems approach revealsregulatory circuitry for Arabidopsis trichome initiation by theGL3 and GL1 selectors. PLoS Genet 2009, 5:e1000396.

44.�

Bramsiepe J, Wester K, Weinl C, Roodbarkelari F, Kasili R,Larkin JC, Hulskamp M, Schnittger A: Endoreplication controlscell fate maintenance. PLoS Genet 2010, 6:e1000996.










































































































http://dx.doi.org/10.1111/nph.12473

















This genetic study underlines the importance of endocycles for themaintenance of cell fate and specification in trichomes using variouscombinations of loss-and-gain of function mutants. Initiated trichomesthat fail to establish endocycles abort further trichome differentiation andeven trans-differentiate into epidermal pavement cells.

45. Kasili R, Huang CC, Walker JD, Simmons LA, Zhou J, Faulk C,Hulskamp M, Larkin JC: BRANCHLESS TRICHOMES links cellshape and cell cycle control in Arabidopsis trichomes.Development 2011, 138:2379-2388.

46. Ishida T, Adachi S, Yoshimura M, Shimizu K, Umeda M,Sugimoto K: Auxin modulates the transition from the mitoticcycle to the endocycle in Arabidopsis. Development 2010,137:63-71.

47. Dello Ioio R, Linhares FS, Scacchi E, Casamitjana-Martinez E,Heidstra R, Costantino P, Sabatini S: Cytokinins determineArabidopsis root-meristem size by controlling celldifferentiation. Curr Biol 2007, 17:678-682.

48. Dello Ioio R, Nakamura K, Moubayidin L, Perilli S, Taniguchi M,Morita MT, Aoyama T, Costantino P, Sabatini S: A geneticframework for the control of cell division and differentiation inthe root meristem. Science 2008, 322:1380-1384.

49.��

Takahashi N, Kajihara T, Okamura C, Kim Y, Katagiri Y,Okushima Y, Matsunaga S, Hwang I, Umeda M: Cytokininscontrol endocycle onset by promoting the expression of anAPC/C activator in Arabidopsis roots. Curr Biol 2013 http://dx.doi.org/10.1016/j.cub.2013.07.051.

The onset of endocycles and cell differentiation coincide during Arabi-dopsis root development. This study demonstrates that the transcriptionfactor ARR2 induces endocycle onset by transcriptional activation of theAPC/C activator CCS52A1. In combination with the study in Ref. [48] thisstudy demonstrates how closely endocycles and differentiation are linkedby cytokinin signalling during plant development.

50. Claeys H, Skirycz A, Maleux K, Inze D: DELLA signaling mediatesstress-induced cell differentiation in Arabidopsis leavesthrough modulation of anaphase-promoting complex/cyclosome activity. Plant Physiol 2012, 159:739-747.

51. Moubayidin L, Perilli S, Dello Ioio R, Di Mambro R, Costantino P,Sabatini S: The rate of cell differentiation controls theArabidopsis root meristem growth phase. Curr Biol 2010,20:1138-1143.

52. Achard P, Gusti A, Cheminant S, Alioua M, Dhondt S, Coppens F,Beemster GTS, Genschik P: Gibberellin signaling controls cellproliferation rate in Arabidopsis. Curr Biol 2009, 19:1188-1193.


53. Ubeda-Tomas S, Federici F, Casimiro I, Beemster GTS,Bhalerao R, Swarup R, Doerner P, Haseloff J, Bennett MJ:Gibberellin signaling in the endodermis controls Arabidopsisroot meristem size. Curr Biol 2009, 19:1194-1199.

54. Ubeda-Tomas S, Swarup R, Coates J, Swarup K, Laplaze L,Beemster GT, Hedden P, Bhalerao R, Bennett MJ: Root growth inArabidopsis requires gibberellin/DELLA signalling in theendodermis. Nat Cell Biol 2008, 10:625-628.

55. Daviere JM, Achard P: Gibberellin signaling in plants.Development 2013, 140:1147-1151.

56. Achard P, Genschik P: Releasing the brakes of plant growth: howGAs shutdown DELLA proteins. J Exp Bot 2009, 60:1085-1092.

57. Ubeda-Tomas S, Beemster GT, Bennett MJ: Hormonalregulation of root growth: integrating local activities intoglobal behaviour. Trends Plant Sci 2012, 17:326-331.

58. Radziejwoski A, Vlieghe K, Lammens T, Berckmans B, Maes S,Jansen MA, Knappe C, Albert A, Seidlitz HK, Bahnweg G et al.:Atypical E2F activity coordinates PHR1 photolyase genetranscription with endoreduplication onset. EMBO J 2011,30:355-363.

59. Berckmans B, Lammens T, Van Den Daele H, Magyar Z, Bogre L,De Veylder L: Light-dependent regulation of DEL1 isdetermined by the antagonistic action of E2Fb and E2Fc. PlantPhysiol 2011, 157:1440-1451.

60. de Almeida Engler J, Kyndt T, Vieira P, Van Cappelle E, Boudolf V,Sanchez V, Escobar C, De Veylder L, Engler G, Abad P et al.:CCS52 and DEL1 genes are key components of the endocyclein nematode-induced feeding sites. Plant J 2012, 72:185-198.

61. Vieira P, Escudero C, Rodiuc N, Boruc J, Russinova E, Glab N,Mota M, De Veylder L, Abad P, Engler G et al.: Ectopic expressionof Kip-related proteins restrains root-knot nematode-feedingsite expansion. New Phytol 2013, 199:505-519.

62.�

Sterken R, Kiekens R, Boruc J, Zhang F, Vercauteren A,Vercauteren I, De Smet L, Dhondt S, Inze D, De Veylder L et al.:Combined linkage and association mapping reveals CYCD5;1as a quantitative trait gene for endoreduplication inArabidopsis. Proc Natl Acad Sci U S A 2012, 109:4678-4683.

In this study the authors describe an elegant way of mapping theCYCD5;1 gene as a positive factor for endoreduplication in Arabidopsis.Since all previously studied CYCs inhibit the endocycle programme andinduce cell divisions, CYCD5;1 potentially represents a unique memberamongst CYC families.


















http://dx.doi.org/10.1016/j.cub.2013.07.051

http://dx.doi.org/10.1016/j.cub.2013.07.051

















































endocycling in the path of plant development

Documents