Restricting Cell Proliferation Research Articles

The dual role of casein kinase 1, DTG1, in regulating tillering and grain size in rice

Tiller number and grain size are important agronomic traits that determine grain yield in rice. Here, we demonstrate that DEFECTIVE TILLER GROWTH 1 (DTG1), a member of the casein kinase 1 protein family, exerts a co-regulatory effect on tiller number and grain size. We identified a single amino acid substitution in DTG1 (I357K) that caused a decrease in tiller number and an increase in grain size in NIL-dtg1. Genetic analyses revealed that DTG1 plays a pivotal role in regulation of tillering and grain size. The DTG1I357K allelic variant exhibited robust functionality in suppressing tillering. We show that DTG1 is preferentially expressed in tiller buds and young panicles, and negatively regulates grain size by restricting cell proliferation in spikelet hulls. We further confirm that DTG1 functioned in grain size regulation by directly interacting with Grain Width 2 (GW2), a critical grain size regulator in rice. The CRISPR/Cas9-mediated elimination of DTG1 significantly enhanced tiller number and grain size, thereby increasing rice grain yield under field conditions, thus highlighting potential value of DTG1 in rice breeding.

OsMADS5 interacts with OsSPL14/17 to inhibit rice root elongation by restricting cell proliferation of root meristem under ammonium supply.

Nitrogen (N) is a vital major nutrient for rice (Oryza sativa). Rice responds to different applications of N by altering its root morphology, including root elongation. Although ammonium ( ) is the primary source of N for rice, is toxic to rice roots and inhibits root elongation. However, the precise molecular mechanism that -inhibited root elongation of rice is not well understood. Here, we identified a rice T-DNA insert mutant of OsMADS5 with a longer seminal root (SR) under sufficient N conditions. Reverse-transcription quantitative PCR analysis revealed that the expression level of OsMADS5 was increased under compared with supply. Under conditions, knocking out OsMADS5 (cas9) produced a longer SR, phenocopying osmads5, while there was no significant difference in SR length between wild-type and cas9 under supply. Moreover, OsMADS5-overexpression plants displayed the opposite SR phenotype. Further study demonstrated that enhancement of OsMADS5 by supply inhibited rice SR elongation, likely by reducing root meristem activity of root tip, with the involvement of OsCYCB1;1. We also found that OsMADS5 interacted with OsSPL14 and OsSPL17 (OsSPL14/17) to repress their transcriptional activation by attenuating DNA binding ability. Moreover, loss of OsSPL14/17 function in osmads5 eliminated its stimulative effect on SR elongation under conditions, implying OsSPL14/17 may function downstream of OsMADS5 to mediate rice SR elongation under supply. Overall, our results indicate the existence of a novel modulatory pathway in which enhancement of OsMADS5 by supply represses the transcriptional activities of OsSPL14/17 to restrict SR elongation of rice.

Deletion of Cd44 Inhibits Metastasis Formation of Liver Cancer in Nf2-Mutant Mice.

Primary liver cancer is the third leading cause of cancer-related death worldwide. An increasing body of evidence suggests that the Hippo tumor suppressor pathway plays a critical role in restricting cell proliferation and determining cell fate during physiological and pathological processes in the liver. Merlin (Moesin-Ezrin-Radixin-like protein) encoded by the NF2 (neurofibromatosis type 2) gene is an upstream regulator of the Hippo signaling pathway. Targeting of Merlin to the plasma membrane seems to be crucial for its major tumor-suppressive functions; this is facilitated by interactions with membrane-associated proteins, including CD44 (cluster of differentiation 44). Mutations within the CD44-binding domain of Merlin have been reported in many human cancers. This study evaluated the relative contribution of CD44- and Merlin-dependent processes to the development and progression of liver tumors. To this end, mice with a liver-specific deletion of the Nf2 gene were crossed with Cd44-knockout mice and subjected to extensive histological, biochemical and molecular analyses. In addition, cells were isolated from mutant livers and analyzed by in vitro assays. Deletion of Nf2 in the liver led to substantial liver enlargement and generation of hepatocellular carcinomas (HCCs), intrahepatic cholangiocarcinomas (iCCAs), as well as mixed hepatocellular cholangiocarcinomas. Whilst deletion of Cd44 had no influence on liver size or primary liver tumor development, it significantly inhibited metastasis formation in Nf2-mutant mice. CD44 upregulates expression of integrin β2 and promotes transendothelial migration of liver cancer cells, which may facilitate metastatic spreading. Overall, our results suggest that CD44 may be a promising target for intervening with metastatic spreading of liver cancer.

MYC-Induced Upregulation of Lncrna ELFN1-AS1 Contributes to Tumor Growth in Colorectal Cancer via Epigenetically Silencing TPM1.

This study revealed a novel molecular pathway in colorectal cancer progression, which may provide new method for early diagnosis and treatment of colorectal cancer.

LncRNA FENDRR Servers as a Possible Marker of Essential Hypertension and Regulates Human Umbilical Vein Endothelial Cells Dysfunction via miR-423-5p/Nox4 Axis.

PurposeEssential hypertension (EH) is an intricate non-communicable infirmity and lncRNAs are validated as essential mediators in EH. The study aimed to propose the expression pattern of FENDRR and miR-423-5p, substantiate the potential mechanism of FENDRR/miR-423-5p/Nox4 axis in EH.Patients and MethodsThe expression of FENDRR and miR-423-5p was evaluated by qRT-PCR and the clinical significance was explored by the ROC curve. Pearson correlation indicated the relationship between FENDRR and miR-423-5p. The function of FENDRR and miR-423-5p on HUVECs was clarified by CCK-8 assay, Transwell assay, and flow cytometry. Western blot was used to assess the relative protein expression of Nox4.ResultsFENDRR was highly expressed and miR-423-5p was lowly expressed in EH patients and a negative correlation between them was determined. FENDRR might serve as a predictive diagnosis in differentiating EH patients. Knockdown of FENDRR or overexpression of miR-423-5p showed expansionary effects in cell proliferation, cell migration, and inhibiting cell apoptosis. Meanwhile, miR-423-5p was determined as a target of FENDRR and mediated the function of FENDRR on HUVECs. Moreover, Nox4 is a down-streaming target gene of miR-423-5p. The protein expression of Nox4 was regulated by the alternation of miR-423-5p expression.ConclusionFENDRR played an energetic role in EH and contributed to HUVECs dysfunction by restricting cell proliferation, suppressing cell migration, and accelerating cell apoptosis by manipulating the miR-423-5p/Nox4 axis.

Abstract P1-08-22: The role of DAXX as a critical growth regulator of triple negative breast cancer

Abstract Background: Triple negative breast cancer (TNBC) is a heterogeneous disease that frequently presents at a metastatic stage or upon initial early stage diagnosis, and may recur quickly. Treatment options are limited outside of cytotoxic chemotherapy in the adjuvant or metastatic setting and there is an immediate need to identify and validate novel biomarkers that predict sensitivity to chemotherapy. Previously, it was shown that the pro-apoptotic protein DAXX is required for paclitaxel-mediated breast cancer cell death. Based on these data and our recent discoveries that DAXX is a potent inhibitor of breast cancer stem cells in ER+ breast cancer (Peiffer et al., Cancer Res. 2019; Peiffer et al., NPJ Breast Cancer. 2020), we next explored the role of DAXX in TNBC. We found that high DAXX expression in TNBC cells regulates cell proliferation and activities of PARP-1 and JNK; two pathways required for cell death. The goals of the current work were to investigate the mechanism by which DAXX regulates proliferation at the level of PARP-1 and/or JNK and test if DAXX expression predicts sensitivity to carboplatin, paclitaxel, doxorubicin, the PARP-1 inhibitor olaparib, or the JNK inhibitor SP600125 in TNBC cells. Methods: Proliferation and cell cycle analysis were performed in three TNBC cell lines (MDA-MB-231, BT549, and MDA-MB-468) under DAXX expression and depletion conditions using an siRNA approach. Sensitivity to carboplatin, paclitaxel, and doxorubicin was determined by measuring proliferation in a dose-dependent manner. PARP-1 activity was assessed by detecting global protein PARylation levels using Western blotting. JNK activation was analyzed by measuring phosphorylated JNK levels. A JNK inhibitor (SP600125) was used to determine if JNK signaling was responsible for restricting cell proliferation and if DAXX was required for the elevated JNK activity. Olaparib was used to assess the role of PARP-1 activation in DAXX-depleted cells. Results: The TNBC cell lines expressed high levels of DAXX. Depletion of DAXX increased cell proliferation by promoting cell cycle progression through the S-phase. The consequence of this increased cell proliferation was decreased sensitivity to carboplatin and paclitaxel, but not to doxorubicin. Mechanistically, at least one chemotherapeutic agent, carboplatin induced JNK activation and DAXX was required for the increased JNK activity. The JNK inhibitor (SP600125) partially reversed resistance to carboplatin in DAXX-depleted cells. Additionally, genetic knockdown of DAXX resulted in elevated PARP-1 activity as measured by global PARylation of proteins. PARP-1 blockade using olaparib also partially reversed resistance to carboplatin in DAXX-depleted cells. Conclusions: These results suggest that DAXX is a critical growth regulator and predictor of response to carboplatin and paclitaxel in triple negative breast cancer cells. DAXX is necessary to activate the JNK pathway in response to carboplatin and it is this carboplatin-mediated JNK signaling that inhibits cell proliferation. Furthermore, DAXX limits PARP-1 activity and is necessary for increased sensitivity to carboplatin or paclitaxel. Data herein support assessing DAXX expression in triple negative tumors to determine if high DAXX expression predicts increased sensitivity to carboplatin, paclitaxel, and if DAXX-low expressing TNBC cells require addition of a JNK or PARP-1 inhibitor. Citation Format: Clodia Osipo, Debra Wyatt, Michelle Fernandez, Daniel S Peiffer, Kathy S Albain. The role of DAXX as a critical growth regulator of triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-22.

Inhibitory effect of selected Indian honey on colon cancer cell growth by inducing apoptosis and targeting the β-catenin/Wnt pathway.

Colon cancer is the most prevalent cause of death from cancer across the globe. Although chemotherapy drugs are predominantly used, their toxicity always remains a cause of concern. As an alternative to synthetic drugs, natural compounds or nutraceuticals are comparatively less toxic. Honey is widely used across different cultures as an alternative form of medicine. It represents a prominent source of plant-phenolic compounds and there is demonstrable evidence of its anti-oxidant and anti-microbial activities. The aim of the present work was to investigate the anti-proliferative effect of some Indian honeys and analyze their mechanism of action in colon cancer. In order to establish the composition-activity relationship, we evaluated the bioactive components present in selected honey samples by GC-MS and HPLC analysis. Indian honey samples showed a significant inhibitory impact on cell growth by restricting cell proliferation, causing apoptosis, and restricting the cell cycle in the G2/M phase specifically for colon cancer cells. The apoptotic activities, as imparted by the honey samples, were established by Annexin V/PI staining, real-time PCR, and immunoblot analyses. The treated cells showed increased expressions of p53 and caspases 3, 8, and 9, thus indicating the involvement of both extrinsic and intrinsic apoptotic pathways. The honey samples were also found to inhibit the β-catenin/Wnt pathway. In the next phase of the study, the efficacy of these honey samples was evaluated in colon carcinoma induced SD-rats. Overall, these findings demonstrated that selected Indian honeys could be established as effective nutraceuticals for the prevention as well as cure of colon cancer.

Androgen receptor (AR) heterogeneity in prostate cancer and therapy resistance.

Androgen receptor (AR), a ligand-dependent nuclear transcription factor and a member of steroid hormone receptor family, plays an important role in prostate organogenesis by regulating epithelial differentiation and restricting cell proliferation. Although rarely mutated or amplified in treatment-naïve prostate cancer (PCa), AR signaling drives tumor growth and as a result, therapies that aim to inhibit AR signaling, called ARSIs (AR signaling inhibitors), have been in clinical use for >70 years. Unfortunately, the clinical efficacy of ARSIs is short-lived and the majority of treated patients develop castration-resistant PCa (CRPC). Numerous molecular mechanisms have been proposed for castration resistance; however, the cellular basis for CRPC emergence has remained obscure. One under-appreciated cellular mechanism for CRPC development is the AR heterogeneity that pre-exists in treatment-naive primary tumors, i.e., although most PCa cells express AR (i.e., AR+), there is always a population of PCa cells that express no/low AR (i.e., AR-/lo). Importantly, this AR heterogeneity becomes accentuated during ARSI treatment and highly prominent in established CRPC. Here, we provide a succinct summary of AR heterogeneity across the PCa continuum and discuss its impact on PCa response to treatments. While AR+ PCa cells/clones exhibit exquisite sensitivities to ARSIs, AR-/lo PCa cells/clones, which are greatly enriched in stem cell signaling pathways, display de novo resistance to ARSIs. Finally, we offer several potential combinatorial strategies, e.g., ARSIs with stem cell targeting therapeutics, to co-target both AR+ and AR-/lo PCa cells and metastatic clones.

GROWTH-REGULATING FACTOR 9 negatively regulates arabidopsis leaf growth by controlling ORG3 and restricting cell proliferation in leaf primordia.

Leaf growth is a complex process that involves the action of diverse transcription factors (TFs) and their downstream gene regulatory networks. In this study, we focus on the functional characterization of the Arabidopsis thaliana TF GROWTH-REGULATING FACTOR9 (GRF9) and demonstrate that it exerts its negative effect on leaf growth by activating expression of the bZIP TF OBP3-RESPONSIVE GENE 3 (ORG3). While grf9 knockout mutants produce bigger incipient leaf primordia at the shoot apex, rosette leaves and petals than the wild type, the sizes of those organs are reduced in plants overexpressing GRF9 (GRF9ox). Cell measurements demonstrate that changes in leaf size result from alterations in cell numbers rather than cell sizes. Kinematic analysis and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay revealed that GRF9 restricts cell proliferation in the early developing leaf. Performing in vitro binding site selection, we identified the 6-base motif 5'-CTGACA-3' as the core binding site of GRF9. By global transcriptome profiling, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) we identified ORG3 as a direct downstream, and positively regulated target of GRF9. Genetic analysis of grf9 org3 and GRF9ox org3 double mutants reveals that both transcription factors act in a regulatory cascade to control the final leaf dimensions by restricting cell number in the developing leaf.

GROWTH-REGULATING FACTOR 9 negatively regulates arabidopsis leaf growth by controlling ORG3 and restricting cell proliferation in leaf primordia

GROWTH-REGULATING FACTOR 9 negatively regulates arabidopsis leaf growth by controlling ORG3 and restricting cell proliferation in leaf primordia

A mitogen-activated protein kinase phosphatase influences grain size and weight in rice.

Grain size and weight are directly associated with grain yield in crops. However, the molecular mechanisms that set final grain size and weight remain largely unknown. Here, we characterize two large grain mutants, large grain8-1 (large8-1) and large grain8-2 (large8-2). LARGE8 encodes the mitogen-activated protein kinase phosphatase1 (OsMKP1). Loss of function mutations in OsMKP1 results in large grains, while overexpression of OsMKP1 leads to small grains. OsMKP1 determines grain size by restricting cell proliferation in grain hulls. OsMKP1 directly interacts with and deactivates the mitogen-activated protein kinase 6 (OsMAPK6). Taken together, we identify OsMKP1 as a crucial factor that influences grain size by deactivating OsMAPK6, indicating that the reversible phosphorylation of OsMAPK6 plays important roles in determining grain size in rice.

P14ARF interacts with the focal adhesion kinase and protects cells from anoikis

The ARF protein functions as an important sensor of hyper-proliferative stimuli restricting cell proliferation through both p53-dependent and -independent pathways. Although to date the majority of studies on ARF have focused on its anti-proliferative role, few studies have addressed whether ARF may also have pro-survival functions. Here we show for the first time that during the process of adhesion and spreading ARF re-localizes to sites of active actin polymerization and to focal adhesion points where it interacts with the phosphorylated focal adhesion kinase. In line with its recruitment to focal adhesions, we observe that hampering ARF function in cancer cells leads to gross defects in cytoskeleton organization resulting in apoptosis through a mechanism dependent on the Death-Associated Protein Kinase. Our data uncover a novel function for p14ARF in protecting cells from anoikis that may reflect its role in anchorage independence, a hallmark of malignant tumor cells.

The INDETERMINATE DOMAIN Protein BROAD LEAF1 Limits Barley Leaf Width by Restricting Lateral Proliferation

Variation in the size, shape, and positioning of leaves as the major photosynthetic organs strongly impacts crop yield, and optimizing these aspects is a central aim of cereal breeding [1, 2]. Leaf growth in grasses is driven by cell proliferation and cell expansion in a basal growth zone [3]. Although several factors influencing final leaf size and shape have been identified from rice and maize [4-14], what limits grass leaf growth in the longitudinal or transverse directions during leaf development remains poorly understood. To identify factors involved in this process, we characterized the barley mutant broad leaf1 (blf1). Mutants form wider but slightly shorter leaves due to changes in the numbers of longitudinal cell files and of cells along the leaf length. These differences arise during primordia outgrowth because of more cell divisions in the width direction increasing the number of cell files. Positional cloning, analysis of independent alleles, and transgenic complementation confirm that BLF1 encodes a presumed transcriptional regulator of the INDETERMINATE DOMAIN family. In contrast to loss-of-function mutants, moderate overexpression of BLF1 decreases leaf width below wild-type levels. A functional BLF1-vYFP fusion protein expressed from the endogenous promoter shows a dynamic expression pattern in the shoot apical meristem and young leaf primordia. Thus, we propose that the BLF1 gene regulates barley leaf size by restricting cell proliferation in the leaf-width direction. Given the agronomic importance of canopy traits in cereals, identifying functionally different BLF1 alleles promises to allow for the generation of optimized cereal ideotypes.

AMPK modulates Hippo pathway activity to regulate energy homeostasis.

The Hippo pathway was discovered as a conserved tumour suppressor pathway restricting cell proliferation and apoptosis. However, the upstream signals that regulate the Hippo pathway in the context of organ size control and cancer prevention are largely unknown. Here, we report that glucose, the ubiquitous energy source utilised for ATP generation, regulates the Hippo pathway downstream effector YAP. We show that both the Hippo pathway and AMP-activated protein kinase (AMPK) were activated during glucose starvation, resulting in phosphorylation of YAP and contributing to its inactivation. We also identified glucose-transporter 3 (GLUT3) as a YAP-regulated gene involved in glucose metabolism. Together, these results demonstrate that glucose-mediated energy homeostasis is an upstream event involved in regulation of the Hippo pathway and, potentially, an oncogenic function of YAP in promoting glycolysis, thereby providing an exciting link between glucose metabolism and the Hippo pathway in tissue maintenance and cancer prevention.

The ubiquitin receptors DA1, DAR1, and DAR2 redundantly regulate endoreduplication by modulating the stability of TCP14/15 in Arabidopsis.

Organ growth involves the coordination of cell proliferation and cell growth with differentiation. Endoreduplication is correlated with the onset of cell differentiation and with cell and organ size, but little is known about the molecular mechanisms linking cell and organ growth with endoreduplication. We have previously demonstrated that the ubiquitin receptor DA1 influences organ growth by restricting cell proliferation. Here, we show that DA1 and its close family members DAR1 and DAR2 are redundantly required for endoreduplication during leaf development. DA1, DAR1, and DAR2 physically interact with the transcription factors TCP14 and TCP15, which repress endoreduplication by directly regulating the expression of cell-cycle genes. We also show that DA1, DAR1, and DAR2 modulate the stability of TCP14 and TCP15 proteins in Arabidopsis thaliana. Genetic analyses demonstrate that DA1, DAR1, and DAR2 function in a common pathway with TCP14/15 to regulate endoreduplication. Thus, our findings define an important genetic and molecular mechanism involving the ubiquitin receptors DA1, DAR1, and DAR2 and the transcription factors TCP14 and TCP15 that links endoreduplication with cell and organ growth.

Transcription factors SOD7/NGAL2 and DPA4/NGAL3 act redundantly to regulate seed size by directly repressing KLU expression in Arabidopsis thaliana.

Although seed size is one of the most important agronomic traits in plants, the genetic and molecular mechanisms that set the final size of seeds are largely unknown. We previously identified the ubiquitin receptor DA1 as a negative regulator of seed size, and the Arabidopsis thaliana da1-1 mutant produces larger seeds than the wild type. Here, we describe a B3 domain transcriptional repressor NGATHA-like protein (NGAL2), encoded by the suppressor of da1-1 (SOD7), which acts maternally to regulate seed size by restricting cell proliferation in the integuments of ovules and developing seeds. Overexpression of SOD7 significantly decreases seed size of wild-type plants, while the simultaneous disruption of SOD7 and its closest homolog DEVELOPMENT-RELATED PcG TARGET IN THE APEX4 (DPA4/NGAL3) increases seed size. Genetic analyses indicate that SOD7 and DPA4 act in a common pathway with the seed size regulator KLU to regulate seed growth, but do so independently of DA1. Further results show that SOD7 directly binds to the promoter of KLUH (KLU) in vitro and in vivo and represses the expression of KLU. Therefore, our findings reveal the genetic and molecular mechanisms of SOD7, DPA4, and KLU in seed size regulation and suggest that they are promising targets for seed size improvement in crops.

Structural dissection of Hippo signaling.

The Hippo pathway controls cell number and organ size by restricting cell proliferation and promoting apoptosis, and thus is a key regulator in development and homeostasis. Dysfunction of the Hippo pathway correlates with many pathological conditions, especially cancer. Hippo signaling also plays important roles in tissue regeneration and stem cell biology. Therefore, the Hippo pathway is recognized as a crucial target for cancer therapy and regeneration medicine. To date, structures of several key components in Hippo signaling have been determined. In this review, we summarize current available structural studies of the Hippo pathway, which may help to improve our understanding of its regulatory mechanisms, as well as to facilitate further functional studies and potential therapeutic interventions.

Control of organ shape and size by YUAN1 in Arabidopsis thaliana

Control of organ shape and size by cell proliferationandcell expansion is a fundamental process in plant development. However, little is known about the molecular mechanisms that set the shape and size of determinate organs in plants. We have previously demonstrated that the Arabidopsis gene DA1 controls the final size of organs by restricting cell proliferation. Through an activation tagging screen for modifiers of da1-1, we have identified a semi-dominant mutant (yuan1-1D) with altered leaf shape and size. The yuan1-1D mutation results in reduced plant height, short and round leaves and short petioles due to defects in cell elongation. YUAN1 encodes a PHD zinc finger domain-containing protein. The GFP-YUAN1 fusion protein is localized to the nucleus. Overexpression of YUAN1 leads to round leaves and short petioles. Genetic analyses show that YUAN1 acts independently of DA1, ROTUNDIFOLIA 3 (ROT3) and ROTUNDIFOLIA4 (ROT4) to influence leaf shape and size. Collectively, our findings show that Arabidopsis YUAN1, a PHD zinc finger domain-containing protein, controls organ shape and size by restricting cell elongation, and give insight into how plants control their organ shape and size.

The Ubiquitin Receptor DA1 Interacts with the E3 Ubiquitin Ligase DA2 to Regulate Seed and Organ Size in Arabidopsis

Seed size in higher plants is determined by the coordinated growth of the embryo, endosperm, and maternal tissue. Several factors that act maternally to regulate seed size have been identified, such as auxin response factor2, apetala2, KLUH, and DA1, but the genetic and molecular mechanisms of these factors in seed size control are almost totally unknown. We previously demonstrated that the ubiquitin receptor DA1 acts synergistically with the E3 ubiquitin ligase enhancer1 OF DA1 (EOD1)/big brother to regulate the final size of seeds in Arabidopsis thaliana. Here, we describe another RING-type protein with E3 ubiquitin ligase activity, encoded by DA2, which regulates seed size by restricting cell proliferation in the maternal integuments of developing seeds. The da2-1 mutant forms large seeds, while overexpression of DA2 decreases seed size of wild-type plants. Overexpression of rice (Oryza sativa) grain width and weight2, a homolog of DA2, restricts seed growth in Arabidopsis. Genetic analyses show that DA2 functions synergistically with DA1 to regulate seed size, but does so independently of EOD1. Further results reveal that DA2 interacts physically with DA1 in vitro and in vivo. Therefore, our findings define the genetic and molecular mechanisms of three ubiquitin-related proteins DA1, DA2, and EOD1 in seed size control and indicate that they are promising targets for crop improvement.

Synthesis of Very-Long-Chain Fatty Acids in the Epidermis Controls Plant Organ Growth by Restricting Cell Proliferation

Author SummaryThe epidermis functions as an important interface with the environment, but in plants it is also essential for establishing and maintaining the primary plant body. Recent studies have shown that the epidermis participates in both driving and restricting plant growth via inter-cell-layer communication. However, it remains an open question as to whether the epidermis can send signals to internal plant tissues to control cell proliferation during development. Here we report that the synthesis of very-long-chain fatty acids (VLCFAs) in the epidermis is essential for the proper control of cell proliferation in the plant Arabidopsis thaliana. We find that defects in VLCFA synthesis cause cells in the vasculature or in the rib zone of shoot apices to overproliferate. When VLCFA levels decrease, we observe that the synthesis of the phytohormone cytokinin increases in the vasculature. We also find that when cytokinin is degraded by the expression of cytokinin oxidase in the vasculature, enhanced cell proliferation in internal tissues is suppressed, indicating that VLCFA synthesis in the epidermis is required to suppress cytokinin biosynthesis and thus cell overproliferation. Our results demonstrate that shoot growth is controlled by interactions between the surface (epidermis) and the axis (vasculature) of the plant body, and highlight a role for VLCFAs in this interaction.