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Centrosomes are the main microtubule-organizing centre of animal cells and are important for many critical cellular and developmental processes from cell polarization to cell division. At the core of the centrosome are centrioles, which recruit pericentriolar material to form the centrosome and act as basal bodies to nucleate formation of cilia and flagella. Defects in centriole structure, function and number are associated with a variety of human diseases, including cancer, brain diseases and ciliopathies. In this review, we discuss recent advances in our understanding of how new centrioles are assembled and how centriole number is controlled. We propose a general model for centriole duplication control in which cooperative binding of duplication factors defines a centriole ‘origin of duplication’ that initiates duplication, and passage through mitosis effects changes that license the centriole for a new round of duplication in the next cell cycle. We also focus on variations on the general theme in which many centrioles are created in a single cell cycle, including the specialized structures associated with these variations, the deuterosome in animal cells and the blepharoplast in lower plant cells.

Multiciliated cells (MCCs) are terminally differentiated epithelia that assemble multiple motile cilia used to promote fluid flow. To template these cilia, MCCs dramatically expand their centriole content during a process known as centriole amplification. In cycling cells, the master regulator of centriole assembly Polo-like kinase 4 (PLK4) is essential for centriole duplication; however recent work has questioned the role of PLK4 in centriole assembly in MCCs. To address this discrepancy, we created genetically engineered mouse models and demonstrated that both PLK4 protein and kinase activity are critical for centriole amplification in MCCs. Tracheal epithelial cells that fail centriole amplification accumulate large assemblies of centriole proteins and do not undergo apical surface area expansion. These results show that the initial stages of centriole assembly are conserved between cycling cells and MCCs and suggest that centriole amplification and surface area expansion are coordinated events. Every day, we inhale thousands of viruses, bacteria and pollution particles. To protect against these threats, cells in our airways produce mucus that traps inhaled particles before they reach the lungs. This mucus then needs to be removed to prevent it from becoming a breeding ground for microbes that may cause a respiratory infection. This is the responsibility of cells covered in tiny hair-like structures called cilia that move together to propel the mucus-trapped particles out of the airways. These specialized cells can have up to 300 motile cilia on their surface, which grow from structures called centrioles that then anchor the cilia in place. Multiciliated cells are generated from precursor cells that only have two centrioles. Therefore, as these precursors develop, they must produce large numbers of centrioles, considerably more than other cells that only need a couple of extra centrioles during cell division. However, recent studies have questioned whether the precursors of multiciliated cells rely on the same regulatory proteins to produce centrioles as dividing cells. To help answer this question, LoMastro et al. created genetically engineered mice that lacked or had an inactive form of PLK4, a protein which controls centriole formation in all cell types lacking multiple cilia. This showed that multiciliated cells also need this protein to produce centrioles. LoMastro et al. also found that multiciliated cells became larger while building centrioles, suggesting that this amplification process helps control the cell’s final size. Defects in motile cilia activity can lead to fluid build-up in the brain, respiratory infections and infertility. Unfortunately, these disorders are difficult to diagnose currently and there is no cure. The findings of LoMastro et al. further our understanding of how motile cilia are built and maintained, and may help future scientists to develop better diagnostic tools and treatments for patients.

Multiciliated cells (MCC) contain hundreds of motile cilia used to propel fluid over their surface. To template these cilia, each MCC produces between 100-600 centrioles by a process termed centriole amplification. Yet, how MCC regulate the precise number of centrioles and cilia remains unknown. Airway progenitor cells contain two parental centrioles (PC) and form structures called deuterosomes that nucleate centrioles during amplification. Using an ex vivo airway culture model, we show that ablation of PC does not perturb deuterosome formation and centriole amplification. In contrast, loss of PC caused an increase in deuterosome and centriole abundance, highlighting the presence of a compensatory mechanism. Quantification of centriole abundance in vitro and in vivo identified a linear relationship between surface area and centriole number. By manipulating cell size, we discovered that centriole number scales with surface area. Our results demonstrate that a cell-intrinsic surface area-dependent mechanism controls centriole and cilia abundance in multiciliated cells.

Multiciliated cells rely on the same master regulator as dividing cells to amplify the number of centrioles needed to generate the hair-like structures that coat their cell surface.Multiciliated cells rely on the same master regulator as dividing cells to amplify the number of centrioles needed to generate the hair-like structures that coat their cell surface.

Multiciliated cells (MCCs) have several hair-like structures called cilia, which are required to propel substances on their surface. A cilium is organized from a basal body which resembles a hollow microtubule structure called a centriole. In terminally differentiated MCCs, hundreds of new basal bodies/centrioles are formed via two parallel pathways: the centriole- and deuterosome-dependent pathways. The deuterosome-dependent pathway is also referred to as “de novo” because unlike the centriole-dependent pathway which requires pre-existing centrioles, in the de novo pathway multiple new centrioles are organized around non-microtubule structures called deuterosomes. In the last five years, some deuterosome-specific markers have been identified and concurrent advancements in the super-resolution techniques have significantly contributed to gaining insights about the major stages of centriole amplification during ciliogenesis. Altogether, a new picture is emerging which also challenges the previous notion that deuterosome pathway is de novo. This review is primarily focused on studies that have contributed towards the better understanding of deuterosome-dependent centriole amplification and presents a developing model about the major stages identified during this process.

Accumulating studies have shown that methylation of tumor suppressor genes plays an important role in tumorigenesis. Deuterosome assembly protein 1 (DEUP1) has been implicated as a suppressor gene in some tumors and promoter methylation led to silencing of its expression. However, the roles of DEUP1 promoter methylation and expression in hepatocellular carcinoma (HCC) are not clear. In the present study, the expression and methylation of the DEUP1 promoter in HCC was investigated and the correlations with HCC occurrence and development were explored. A total of 60 HCC tumor and adjacent non-tumor tissues were included in this study. Reverse transcription-polymerase chain reaction, bisulfite PCR sequencing, immunohistochemistry and western blotting were applied to detect the methylation status of the DEUP1 promoter and its expression, and to analyze their associations with clinicopathological data. The results showed that the mRNA and protein expression of DEUP1 in adjacent non-tumor tissues was significantly increased compared with in the HCC tissues. DEUP1 promoter methylation was detected in 46/60 (76.7%) tumor tissues and there was a negative correlation between promoter methylation and DEUP1 protein expression (P<0.05). Analysis of the clinicopathological data revealed that the mRNA and protein expression of DEUP1, and its promoter methylation status, was associated with tumor node metastasis stage and tumor differentiation. Taken together, the results of the present study suggested that methylation of the DEUP1 promoter maybe an important mechanism for gene inactivation and has a critical role in the occurrence and development of liver cancer.

The deuterosome is a non-membranous organelle involved in large-scale centriole amplification during multiciliogenesis. Deuterosomes are specifically assembled during the process of multiciliogenesis. However, the molecular mechanisms underlying deuterosome formation are poorly understood. In this study, we investigated the molecular properties of deuterosome protein 1 (Deup1), an essential protein involved in deuterosome assembly. We found that Deup1 has the ability to self-assemble into macromolecular condensates both in vitro and in cells. The Deup1-containing structures formed in multiciliogenesis and the Deup1 condensates self-assembled in vitro showed low turnover of Deup1, suggesting that Deup1 forms highly stable structures. Our biochemical analyses revealed that an increase of the concentration of Deup1 and a crowded molecular environment both facilitate Deup1 self-assembly. The self-assembly of Deup1 relies on its N-terminal region, which contains multiple coiled coil domains. Using an optogenetic approach, we demonstrated that self-assembly and the C-terminal half of Deup1 were sufficient to spatially compartmentalize centrosomal protein 152 (Cep152) and polo like kinase 4 (Plk4), master components for centriole biogenesis, in the cytoplasm. Collectively, the present data suggest that Deup1 forms the structural core of the deuterosome through self-assembly into stable macromolecular condensates. This article has an associated First Person interview with the first author of the paper.

Xenopus has been one of the earliest and most important vertebrate model organisms for investigating the role and structure of basal bodies. Early transmission electron microscopy studies in Xenopus revealed the fine structures of Xenopus basal bodies and their accessory structures. Subsequent investigations using multiciliated cells in the Xenopus epidermis have further revealed many important features regarding the transcriptional regulation of basal body amplification as well as the regulation of basal body/cilia polarity. Future basal body research using Xenopus is expected to focus on the application of modern genome editing techniques (CRISPR/TALEN) to characterize the components of basal body proteins and their molecular functions.