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The article investigates the essence of political and communicative space, the mechanisms of its formation and channels of influence on public opinion. Disclosed are its universal characteristics: multidimensionality, heterogeneity and its role in legitimizing the ruling political regime. Underlines the relationship of effective communication with resource base of communicator and socio-political order of representative social and political groups.

In the article the formation of basic approaches to the study of the specific character of domestic provincial culture is outlined. The analysis of the state of contemporary studies on this problems is undertaken. Key directions in the study of the phenomenon of the provincial culture of Russia are revealed.

Meiosis, endoreplication, and asynthetic fissions are variations of the canonical cell cycle where either replication or mitotic divisions are muted. Here, we identify a cell cycle variantconserved across organs and mammals, where both replication and mitosis are muted, and that orchestrates the differentiation of post-mitotic progenitors into multiciliated cells (MCCs). MCC progenitors reactivate most of the cell cycle transcriptional program but replace the temporal expression of cyclins E2 and A2 with non-canonical cyclins O and A1. In addition, the primary APC/C inhibitor Emi1 is silenced. Re-expressing cyclins E2 and A2 and/or Emi1 can induce partial replication or mitosis. This shows that a cell can co-opt the cell cycle genetic program and regulate only certain elements to qualitatively and quantitatively divert CDK activity toward differentiation rather than division. We propose this cell cycle variant to exploit the existence of a cytoplasmic-or centriolar-CDK threshold lower than the S-phase threshold., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Multiciliated cells (MCCs) ensure fluid circulation in various organs. Their differentiation is marked by the amplification of cilia-nucleating centrioles, driven by a genuine cell-cycle variant, which is characterized by wave-like expression of canonical and non-canonical cyclins such as Cyclin O (CCNO). Patients with CCNO mutations exhibit a subtype of primary ciliary dyskinesia called reduced generation of motile cilia (RGMC). Here, we show that Ccno is activated at the crossroads of the onset of MCC differentiation, the entry into the MCC cell-cycle variant, and the activation of the centriole biogenesis program. Its absence blocks the G 1 /S-like transition of the cell-cycle variant, interrupts the centriologenesis transcription program, and compromises the production of centrioles and cilia in mouse brain and human respiratory MCCs. Altogether, our study identifies CCNO as a core regulator of entry into the MCC cell-cycle variant and the interruption of this variant as one etiology of RGMC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ependymal cells (ECs) are multiciliated cells in the brain that contribute to cerebrospinal fluid flow. ECs are specified during embryonic stages but differentiate later in development. Their differentiation depends on genes such as GEMC1 and MCIDAS in conjunction with E2F4/5 as well as on cell-cycle-related factors. In the mouse brain, we observe that nuclear deformation accompanies EC differentiation. Tampering with these deformations either by decreasing F-actin levels or by severing the link between the nucleus and the actin cytoskeleton blocks differentiation. Conversely, increasing F-actin by knocking out the Arp2/3 complex inhibitor Arpin or artificially deforming the nucleus activates differentiation. These data are consistent with actin polymerization triggering nuclear deformation and jump starting the signaling that produces ECs. A player in this process is the retinoblastoma 1 (RB1) protein, whose phosphorylation prompts MCIDAS activation. Overall, this study identifies a role for actin-based mechanical inputs to the nucleus as controlling factors in cell differentiation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Multiciliated cells (MCC) display on their apical surface hundreds of beating cilia that propel physiological fluids. They line brain ventricles where they propel the cerebrospinal liquid, airways where they clear mucus and pathogens and reproductive ducts where they concentrate the sperm in males or drive the egg along the oviducts in females. Motile cilia are nucleated from basal bodies which are modified centrioles. MCC therefore evade centriole archetypal duplication program to make several hundreds and nucleate an identical number of motile cilia. Defects in this centriole amplification process lead to severe human pathologies called "ciliary aplasia" or "acilia syndrome" and more recently renamed "reduced generation of motile cilia" (RGMC). Patients with this syndrome present frequent hydrocephaly, lung failure, and subfertility. In this manuscript, we describe the protocol we developed and optimized over the years to live image the centriole amplification dynamics. We explain why mouse brain MCC is a good model and provide the tips to enable successful spatially and temporally resolved monitoring of this massive organelle reorganization., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Immune cells sense the microenvironment to fine-tune their inflammatory responses. Patients with cryopyrin-associated periodic syndrome (CAPS), caused by mutations in the NLRP3 gene, develop autoinflammation triggered by nonantigenic cues such as from the environment. However, the underlying mechanisms are poorly understood. Here, we uncover that KCNN4, a calcium-activated potassium channel, links PIEZO-mediated mechanotransduction to NLRP3 inflammasome activation. Yoda1, a PIEZO1 agonist, lowered the threshold for NLRP3 inflammasome activation. PIEZO-mediated sensing of stiffness and shear stress increased NLRP3-dependent inflammation. Myeloid-specific deletion of PIEZO1/2 protected mice from gouty arthritis. Mechanistically, activation of PIEZO1 triggers calcium influx, which activates KCNN4 to evoke potassium efflux and promotes NLRP3 inflammasome activation. Activation of PIEZO signaling was sufficient to activate the inflammasome in cells expressing CAPS-causing NLRP3 mutants via KCNN4. Last, pharmacological inhibition of KCNN4 alleviated autoinflammation in cells of patients with CAPS and in mice bearing a CAPS mutation. Thus, PIEZO-dependent mechanical inputs boost inflammation in NLRP3-dependent diseases, including CAPS.

Cilia are organelles emanating from the cell surface, consisting of an axoneme of microtubules that extends from a basal body derived from the centrioles. They are either isolated and nonmotile (primary cilia), or grouped and motile (motile cilia). Cilia are at the centre of fundamental sensory processes and are involved in a wide range of human disorders. Pulmonary cilia include motile cilia lining the epithelial cells of the conductive airways to orchestrate mucociliary clearance, and primary cilia found on nondifferentiated epithelial and mesenchymal cells acting as sensors and cell cycle keepers. Whereas cilia are essential along the airways, their regulatory molecular mechanisms remain poorly understood, resulting in a lack of therapeutic strategies targeting their structure or functions. This review summarises the current knowledge on cilia in the context of lung homeostasis and COPD to provide a comprehensive overview of the (patho)biology of cilia in respiratory medicine with a particular emphasis on COPD., Competing Interests: Conflict of interest: J-M. Perotin reports lecture honoraria from AstraZeneca, and travel support from Novartis, AstraZeneca and Chiesi, outside the submitted work. D. Al Alam reports grants from NIH/NHLBI R01HL141856, NIH/NHLBI and Office of the Director R21HL165411, outside the submitted work. G. Deslée reports support for attending meetings from Chiesi, and personal fees from Chiesi, Boehringer, GSK and AstraZeneca, outside the submitted work. V. Dormoy reports personal fees from Chiesi, and personal fees from AstraZeneca, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

Choroid plexuses (ChPs) produce cerebrospinal fluid and sense non-cell-autonomous stimuli to control the homeostasis of the central nervous system. They are mainly composed of epithelial multiciliated cells, whose development and function are still controversial. We have thus characterized the stepwise order of mammalian ChP epithelia cilia formation using a combination of super-resolution-microscopy approaches and mouse genetics. We show that ChP ciliated cells are built embryonically on a treadmill of spatiotemporally regulated events, starting with atypical centriole amplification and ending with the construction of nodal-like 9+0 cilia, characterized by both primary and motile features. ChP cilia undergo axoneme resorption at early postnatal stages through a microtubule destabilization process controlled by the microtubule-severing enzyme spastin and mitigated by polyglutamylation levels. Notably, this phenotype is preserved in humans, suggesting a conserved ciliary resorption mechanism in mammals., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cajal-Retzius cells (CRs) are key players in cerebral cortex development, and they display a unique transcriptomic identity. Here, we use scRNA-seq to reconstruct the differentiation trajectory of mouse hem-derived CRs, and we unravel the transient expression of a complete gene module previously known to control multiciliogenesis. However, CRs do not undergo centriole amplification or multiciliation. Upon deletion of Gmnc, the master regulator of multiciliogenesis, CRs are initially produced but fail to reach their normal identity resulting in their massive apoptosis. We further dissect the contribution of multiciliation effector genes and identify Trp73 as a key determinant. Finally, we use in utero electroporation to demonstrate that the intrinsic competence of hem progenitors as well as the heterochronic expression of Gmnc prevent centriole amplification in the CR lineage. Our work exemplifies how the co-option of a complete gene module, repurposed to control a distinct process, may contribute to the emergence of novel cell identities., Competing Interests: Declaration of interests The authors declare no competing interests, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Multiciliated ependymal cells and adult neural stem cells are components of the adult neurogenic niche, essential for brain homeostasis. These cells share a common glial cell lineage regulated by the Geminin family members Geminin and GemC1/Mcidas. Ependymal precursors require GemC1/Mcidas expression to massively amplify centrioles and become multiciliated cells. Here, we show that GemC1-dependent differentiation is initiated in actively cycling radial glial cells, in which a DNA damage response, including DNA replication-associated damage and dysfunctional telomeres, is induced, without affecting cell survival. Genotoxic stress is not sufficient by itself to induce ependymal cell differentiation, although the absence of p53 or p21 in progenitors hinders differentiation by maintaining cell division. Activation of the p53-p21 pathway downstream of GemC1 leads to cell-cycle slowdown/arrest, which permits timely onset of ependymal cell differentiation in progenitor cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Astroblastomas (ABs) are rare brain tumors of unknown origin. We performed an integrative genetic and epigenetic analysis of AB-like tumors. Here, we show that tumors traceable to neural stem/progenitor cells (radial glia) that emerge during early to later brain development occur in children and young adults, respectively. Tumors with MN1-BEND2 fusion appear to present exclusively in females and exhibit overexpression of genes expressed prior to 25 post-conception weeks (pcw), including genes enriched in early ventricular zone radial glia and ependymal tumors. Other, histologically classic ABs overexpress or harbor mutations of mitogen-activated protein kinase pathway genes, outer and truncated radial glia genes, and genes expressed after 25 pcw, including neuronal and astrocyte markers. Findings support that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors. Selective gene fusion, variable imprinting and/or chromosome X-inactivation escape resulting in biallelic overexpression may contribute to female predominance of AB molecular subtypes., (© 2022. The Author(s).)

Exon junction complexes (EJCs) mark untranslated spliced mRNAs and are crucial for the mRNA lifecycle. An imbalance in EJC dosage alters mouse neural stem cell (mNSC) division and is linked to human neurodevelopmental disorders. In quiescent mNSC and immortalized human retinal pigment epithelial (RPE1) cells, centrioles form a basal body for ciliogenesis. Here, we report that EJCs accumulate at basal bodies of mNSC or RPE1 cells and decline when these cells differentiate or resume growth. A high-throughput smFISH screen identifies two transcripts accumulating at centrosomes in quiescent cells, NIN and BICD2. In contrast to BICD2, the localization of NIN transcripts is EJC-dependent. NIN mRNA encodes a core component of centrosomes required for microtubule nucleation and anchoring. We find that EJC down-regulation impairs both pericentriolar material organization and ciliogenesis. An EJC-dependent mRNA trafficking towards centrosome and basal bodies might contribute to proper mNSC division and brain development.

The past two decades have left behind the old conception of early fate-restricted neural progenitors. The new paradigm is that of a more plastic brain, in which the cellular potential of multi-fated progenitors is progressively restricted. This is observed in the switch from neurogenesis to gliogenesis, but also in the generation of different types of glial cells and neurons at later stages. The mechanisms that establish brain cell diversity or heterogeneity within a single population are starting to be elucidated. The role of cell cycle regulators and dynamics and the asymmetric distribution of cell cargoes during cell division are attracting more attention. Understanding these mechanisms could open the way for new treatments against brain pathologies such as brain tumors or neurodegenerative disorders., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In many organs, thousands of microscopic 'motile cilia' beat in a coordinated fashion generating fluid flow. Physiologically, these flows are important in both development and homeostasis of ciliated tissues. Combining experiments and simulations, we studied how cilia from brain tissue align their beating direction. We subjected cilia to a broad range of shear stresses, similar to the fluid flow that cilia themselves generate, in a microfluidic setup. In contrast to previous studies, we found that cilia from mouse ependyma respond and align to these physiological shear stress at all maturation stages. Cilia align more easily earlier in maturation, and we correlated this property with the increase in multiciliated cell density during maturation. Our numerical simulations show that cilia in densely packed clusters are hydrodynamically screened from the external flow, in agreement with our experimental observation. Cilia carpets create a hydrodynamic screening that reduces the susceptibility of individual cilia to external flows., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Cell biology relies largely on reproducible visual observations. Unlike cell culture, tissues are heterogeneous, making difficult the collection of biological replicates that would spotlight a precise location. In consequence, there is no standard approach for estimating the statistical significance of an observed pattern in a tissue sample. Here, we introduce SET (for Synthesis of Epithelial Tissue), a method that can accurately reconstruct the cell tessellation formed by an epithelium in a microscopy image as well as thousands of alternative synthetic tessellations made of the exact same cells. SET can build an accurate null distribution to statistically test if any local pattern is necessarily the result of a process, or if it could be explained by chance in the given context. We provide examples in various tissues where visible, and invisible, cell and subcellular patterns are unraveled in a statistically significant manner using a single image and without any parameter settings.

Motile cilia are widespread across the animal and plant kingdoms, displaying complex collective dynamics central to their physiology. Their coordination mechanism is not generally understood, with previous work mainly focusing on algae and protists. We study here the entrainment of cilia beat in multiciliated cells from brain ventricles. The response to controlled oscillatory external flows shows that flows at a similar frequency to the actively beating cilia can entrain cilia oscillations. We find that the hydrodynamic forces required for this entrainment strongly depend on the number of cilia per cell. Cells with few cilia (up to five) can be entrained at flows comparable to cilia-driven flows, in contrast with what was recently observed in Chlamydomonas Experimental trends are quantitatively described by a model that accounts for hydrodynamic screening of packed cilia and the chemomechanical energy efficiency of the flagellar beat. Simulations of a minimal model of cilia interacting hydrodynamically show the same trends observed in cilia., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

The subventricular zone (SVZ) is one of two main niches where neurogenesis persists during adulthood, as it retains neural stem cells (NSCs) with self-renewal capacity and multi-lineage potency. Another critical cellular component of the niche is the population of postmitotic multiciliated ependymal cells. Both cell types are derived from radial glial cells that become specified to each lineage during embryogenesis. We show here that GemC1, encoding Geminin coiled-coil domain-containing protein 1, is associated with congenital hydrocephalus in humans and mice. Our results show that GemC1 deficiency drives cells toward a NSC phenotype, at the expense of multiciliated ependymal cell generation. The increased number of NSCs is accompanied by increased levels of proliferation and neurogenesis in the postnatal SVZ. Finally, GemC1-knockout cells display altered chromatin organization at multiple loci, further supporting a NSC identity. Together, these findings suggest that GemC1 regulates the balance between NSC generation and ependymal cell differentiation, with implications for the pathogenesis of human congenital hydrocephalus., (© 2019 Wiley Periodicals, Inc.)

Multiciliated cells (MCCs) amplify large numbers of centrioles that convert into basal bodies, which are required for producing multiple motile cilia. Most centrioles amplified by MCCs grow on the surface of organelles called deuterosomes, whereas a smaller number grow through the centriolar pathway in association with the two parent centrioles. Here, we show that MCCs lacking deuterosomes amplify the correct number of centrioles with normal step-wise kinetics. This is achieved through a massive production of centrioles on the surface and in the vicinity of parent centrioles. Therefore, deuterosomes may have evolved to relieve, rather than supplement, the centriolar pathway during multiciliogenesis. Remarkably, MCCs lacking parent centrioles and deuterosomes also amplify the appropriate number of centrioles inside a cloud of pericentriolar and fibrogranular material. These data show that the centriole number is set independently of their nucleation platforms and suggest that massive centriole production in MCCs is a robust process that can self-organize.

Reproductive and respiratory organs, along with brain ventricles, are lined by multiciliated epithelial cells (MCC) that generate cilia-powered fluid flows. MCC hijack the centrosome duplication pathway to form hundreds of centrioles and nucleate motile cilia. In these cells, the large majority of procentrioles are formed associated with partially characterized organelles called deuterosomes. We recently challenged the paradigm that deuterosomes and procentrioles are formed de novo by providing data, in brain MCC, suggesting that they are nucleated from the pre-existing centrosomal younger centriole. However, the origin of deuterosomes and procentrioles is still under debate. Here, we further question centrosome importance for deuterosome and centriole amplification. First, we provide additional data confirming that centriole amplification occurs sequentially from the centrosomal region, and that the first procentriole-loaded deuterosomes are associated with the daughter centriole or in the centrosomal centriole vicinity. Then, to further test the requirement of the centrosome in deuterosome and centriole formation, we depleted centrosomal centrioles using a Plk4 inhibitor. We reveal unexpected limited consequences in deuterosome/centriole number in absence of centrosomal centrioles. Notably, in absence of the daughter centriole only, deuterosomes are not seen associated with the mother centriole. In absence of both centrosomal centrioles, procentrioles are still amplified sequentially and with no apparent structural defects. They seem to arise from a focal region, characterized by microtubule convergence and pericentriolar material (PCM) assembly. The relevance of deuterosome association with the daughter centriole as well as the role of the PCM in the focal and sequential genesis of centrioles in absence of centrosomal centrioles are discussed.

Motile cilia of epithelial multiciliated cells transport vital fluids along organ lumens to promote essential respiratory, reproductive and brain functions. Progenitors of multiciliated cells undergo massive and coordinated organelle remodelling during their differentiation for subsequent motile ciliogenesis. Defects in multiciliated cell differentiation lead to severe cilia-related diseases by perturbing cilia-based flows. Recent work designated the machinery of mitosis as the orchestrator of the orderly progression of differentiation associated with multiple motile cilia formation. By examining the events leading to motile ciliogenesis with a methodological prism of mitosis, we contextualise and discuss the recent findings to broaden the spectrum of questions related to the differentiation of mammalian multiciliated cells., (© 2019 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.)