Regulation of cell cycle in plant gametes: when is the right time to divide?

Abstract

Cell division is a fundamental process shared across diverse life forms, from yeast to humans and plants. Multicellular organisms reproduce through the formation of specialized types of cells, the gametes, which at maturity enter a quiescent state that can last decades. At the point of fertilization, signalling lifts the quiescent state and triggers cell cycle reactivation. Studying how the cell cycle is regulated during plant gamete development and fertilization is challenging, and decades of research have provided valuable, yet sometimes contradictory, insights. This Review summarizes the current understanding of plant cell cycle regulation, gamete development, quiescence, and fertilization-triggered reactivation.

Keywords: Cell cycle; Fertilization; Plant gametes.

Fig. 1.

The cell cycle in Arabidopsis. Graphical representation of the Arabidopsis cell cycle and of its regulators involved in each phase. The phases of the cell cycle (G1-S-G2-M) are represented with arrows, reflecting the unidirectionality of the process. High levels of the cell cycle inhibitors KRPs and RBR1 cause the cell cycle to arrest in the G1 phase by inhibiting CDKA activity and sequestering E2F, thus preventing E2F from activating the genes required for DNA replication. At the G1-S transition, levels of CYC D and A types increase, allowing the formation of CDKA–CYC complexes. With the activating phosphorylation from CAK, CDKA kinase activity is enhanced. CDKA then phosphorylates RBR1, leading to the proteasome-mediated degradation of RBR1. This releases E2F from inhibition, enabling the expression of genes necessary for DNA replication. At the S-G2 boundary, the cellular concentration of CYC A and B types increases, promoting their dimerization with CDKA-B kinases. The activity of the CDKA-B kinases is inhibited by KRPs, and by phosphorylation by WEE1. In the G2 phase, CDKA-B activity is further suppressed by the SIM/SMR inhibitors. However, as the cell prepares for mitosis, phosphorylation of CDKA-B by CAK activates the CDKA-B–CYCB complex, which in turn stimulates the activity of the APC/C complex. The APC/C mediates the ubiquitination of A- and B-type CYCs, leading to their degradation. The destruction of CYCB allows the cell to commit to mitosis. APC/C, ANAPHASE PROMOTING COMPLEX; CDKA, CDKB, CYCLIN-DEPENDENT KINASE A/B type; E2F, E2F TRANSCRIPTION FACTOR; KRP, KIP-RELARED PROTEIN; RBR1, RETINOBLASTOMA RELATED 1; SIM/SMR, SIAMESE/SIAMESE-RELATED; CAK, CDK-ACTIVATING KINASE; WEE1, WEE1 KINASE HOMOLOGUE; P, phosphorylation; Ub, ubiquitination.

Fig. 2.

Male reproductive development in Arabidopsis. (A-D) Graphical summary of the main events during Arabidopsis male reproductive development, and of the cell cycle regulators involved in the meiosis and mitosis events. Pollen development begins in the anthers, where diploid pollen mother cells undergo meiosis to produce four haploid microspores. During meiosis (A), CDKA–CYC complexes phosphorylate a series of target proteins, such as ASY1 and TDM1, which control chromosome axis formation and exit from meiosis. During male gametogenesis, the microspores undergo an asymmetric mitotic division, producing a large vegetative cell and a smaller generative cell. Cell division in the vegetative cell is inhibited by RBR1 and KRPs (B). The generative cell undergoes another round of mitosis, resulting in two sperm cells. This process is mediated by DUO1, which activates the CDKA;1–CYCB complex (C). Both mitotic divisions are regulated by the CDKA;1–CYCD complex. FBL17 facilitates the degradation of KRPs, thereby enabling CDKA;1 activity during the second mitotic division. CDKA;1 activity, in turn, promotes the phosphorylation and degradation of RBR1, thus releasing E2F from inhibition and enabling the expression of genes necessary for DNA replication (D). ASY1, ASYNAPTIC 1; CDKA, CYCLIN-DEPENDENT KINASE A; CYCA/D, CYCLIN A/D-type; E2F, E2F TRANSCRIPTION FACTOR; KRP, KIP-RELATED PROTEIN; RBR1, RETINOBLASTOMA RELATED 1; DUO1, DUO POLLEN 1; FBL17, F-BOX LIKE 17; SCF, SCF ubiquitin ligase complex; TDM1, THREE DIVISION MUTANT 1; P, phosphorylation.

Fig. 3.

Female reproductive development in Arabidopsis. (A,B) Graphical summary of key events during Arabidopsis female reproductive development, and of the cell cycle regulators involved in the meiosis and mitosis events. The megaspore mother cell undergoes meiosis (A), forming a tetrad of haploid spores. KRPs inhibit CDKA;1, allowing RBR1 to accumulate and halt cell cycle progression by directly repressing WUS expression; this absence of WUS in the megaspore mother cell is crucial for limiting mitotic divisions and initiating meiosis. After meiosis, three spores degenerate, while the remaining spore undergoes three rounds of mitosis without cytokinesis (B). The mitotic divisions are orchestrated by CDKA;1–CYCD complexes during G1-S transitions and CDKA-B–CYCB complexes during G2-M transitions. Cellularization then takes place to produce one egg cell (magenta), two synergids (green), three antipodal cells (grey), and a central cell (yellow). The central cell is formed by the fusion of two haploid polar nuclei. APC/C, ANAPHASE PROMOTING COMPLEX; CDKA, CYCLIN-DEPENDENT KINASE A; CYCD, CYCLIN D-type; E2F, E2F TRANSCRIPTION FACTOR; CAK, CDK-ACXTIVATING KINASE; KRP, KIP-RELARED PROTEIN; RBR1, RETINOBLASTOMA RELATED 1; RFCs, REPLICATION FACTORS; WUS, WUSCHEL; P, phosphorylation; Ub, ubiquitination.

Fig. 4.

Alternative models of the cell cycle stage of Arabidopsis gametes at maturity, fertilization and karyogamy. Schematics summarizing alternative models (proposed by Friedman, 1999; Liu et al., 2020; Voichek et al., 2023 and Simonini et al., 2024) of the cell cycle stage of Arabidopsis female and male gametes at maturity, at the moment of fertilization and at karyogamy. Conflicting evidence has led to different models of the state of mature gametes (left panel): central cells (yellow) have been proposed to be in G1 (according to Liu et al. and Voichek et al.) or arrested S (according to Friedman et al. and Simonini et al.); egg cells (red) have been proposed to be in G0 (Voichek et al.), G1 (Liu et al.) or G2 (Friedman et al. and Simonini et al.); sperm cells (green) have been proposed to be in G1 (Liu et al. and Voichek et al.) or G2 (Friedman et al. and Simonini et al.). The progression of events during fertilization and karyogamy (middle and right panels) is closely tied to the cell cycle stages of the fusing gametes. If both gametes are in G1 or G0, DNA synthesis is initiated immediately after fusion, as suggested by studies such as Liu et al. and Voichek et al. For G2-phase gamete fusion, the fertilized gamete transitions directly into mitosis, as proposed in findings by Simonini et al. and Friedman et al. In scenarios where one gamete is in S-phase and the other is in G2, the S-phase gamete must first complete DNA replication to reach G2 before mitosis can proceed, a mechanism described in the context of the central cell by Simonini et al.

Fig. 5.

Cell cycle reactivation in the central cell. Cell cycle progression in the central cell is halted by RBR1 activity (top panel). During karyogamy (bottom panel), the delivery of paternally produced CYCD7;1 protein and its messenger RNA forms an active CDKA;1–CYCD complex. This complex triggers RBR1 degradation, thereby enabling cell cycle progression.