Cilia-based flow network in the brain ventricles

Faubel, Regina; Westendorf, Christian; Bodenschatz, Eberhard; Eichele, Gregor

doi:10.1126/science.aae0450

Cited by 239 publications

(244 citation statements)

References 24 publications

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“…On a control en face lateral ventricle, the beads flowed anteriorly (Fig. 5G,I), consistent with the direction of CSF flow in vivo (Mirzadeh et al 2010a;Faubel et al 2016). In contrast, on a Nestin-Cre; Prdm16 fl/fl lateral ventricle, beads flowed ventrally in the posterior half of the specimen and not in any consistent orientation in the anterior half (Fig.…”

Section: Sox2supporting

confidence: 50%

“…To examine whether Nestin-Cre; Prdm16 fl/fl mice exhibit defects in cilia movement, we added fluorescently labeled microbeads to the lateral ventricle surface of freshly dissected SVZs in culture and analyzed the movement of the beads by live imaging (Mirzadeh et al 2010a;Faubel et al 2016). On a control en face lateral ventricle, the beads flowed anteriorly (Fig.…”

Section: Sox2mentioning

confidence: 99%

“…The SVZ also contains astrocytes, endothelial cells, and ependymal cells, each of which regulates neural stem cell function and neurogenesis (Lim et al 2000;Mirzadeh et al 2008;Porlan et al 2014). Ependymal cells are multiciliated cells that line the walls of the ventricles in the central nervous system (CNS) and promote the directional flow of cerebrospinal fluid (CSF) (Sawamoto et al 2006;Mirzadeh et al 2010b;Faubel et al 2016). CSF contains cytokines that are critical for the maintenance and proliferation of neural stem cells, and CSF flow regulates neuroblast migration (Sawamoto et al 2006).…”

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confidence: 99%

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Prdm16 is required for the maintenance of neural stem cells in the postnatal forebrain and their differentiation into ependymal cells

et al. 2017

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We and others showed previously that PR domain-containing 16 (Prdm16) is a transcriptional regulator required for stem cell function in multiple fetal and neonatal tissues, including the nervous system. However, Prdm16 germline knockout mice died neonatally, preventing us from testing whether Prdm16 is also required for adult stem cell function. Here we demonstrate that Prdm16 is required for neural stem cell maintenance and neurogenesis in the adult lateral ventricle subventricular zone and dentate gyrus. We also discovered that Prdm16 is required for the formation of ciliated ependymal cells in the lateral ventricle. Conditional Prdm16 deletion during fetal development using Nestin-Cre prevented the formation of ependymal cells, disrupting cerebrospinal fluid flow and causing hydrocephalus. Postnatal Prdm16 deletion using Nestin-CreER T2 did not cause hydrocephalus or prevent the formation of ciliated ependymal cells but caused defects in their differentiation. Prdm16 was required in neural stem/ progenitor cells for the expression of Foxj1, a transcription factor that promotes ependymal cell differentiation. These studies show that Prdm16 is required for adult neural stem cell maintenance and neurogenesis as well as the formation of ependymal cells.

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Section: Sox2supporting

confidence: 50%

Section: Sox2mentioning

confidence: 99%

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confidence: 99%

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Prdm16 is required for the maintenance of neural stem cells in the postnatal forebrain and their differentiation into ependymal cells

et al. 2017

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“…The combinatorial powers of ciliary parameters described in our study, such as beat direction, kinematics, and coordination, suggest a richness of potential scenarios for shaping the extracellular fluid environment at multiple scales to drive tissue homeostasis and remodeling, much as described for other tissue-organizing mechanical forces (44). Indeed, new imaging techniques have recently mapped both structurally distinct populations of cilia and spatiotemporally varying ciliary flow dynamics, in the ventricles of the mouse brain (45,46). Multiscale analyses of ciliated tissues not only reveal new tissue-level phenomena, but also enable a quantification of their functional roles in different tissue environments.…”

Section: Discussionmentioning

confidence: 78%

Motile cilia create fluid-mechanical microhabitats for the active recruitment of the host microbiome

Nawroth

Guo

Koch

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

103

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We show that mucociliary membranes of animal epithelia can create fluid-mechanical microenvironments for the active recruitment of the specific microbiome of the host. In terrestrial vertebrates, these tissues are typically colonized by complex consortia and are inaccessible to observation. Such tissues can be directly examined in aquatic animals, providing valuable opportunities for the analysis of mucociliary activity in relation to bacteria recruitment. Using the squid-vibrio model system, we provide a characterization of the initial engagement of microbial symbionts along ciliated tissues. Specifically, we developed an empirical and theoretical framework to conduct a census of ciliated cell types, create structural maps, and resolve the spatiotemporal flow dynamics. Our multiscale analyses revealed two distinct, highly organized populations of cilia on the host tissues. An array of long cilia (∼25 µm) with metachronal beat creates a flow that focuses bacteria-sized particles, at the exclusion of larger particles, into sheltered zones; there, a field of randomly beating short cilia (∼10 µm) mixes the local fluid environment, which contains host biochemical signals known to prime symbionts for colonization. This cilia-mediated process represents a previously unrecognized mechanism for symbiont recruitment. Each mucociliary surface that recruits a microbiome such as the case described here is likely to have system-specific features. However, all mucociliary surfaces are subject to the same physical and biological constraints that are imposed by the fluid environment and the evolutionary conserved structure of cilia. As such, our study promises to provide insight into universal mechanisms that drive the recruitment of symbiotic partners.cilia | microfluidics | host-bacterial symbiosis | biological fluid mechanics, biofiltration M any eukaryotic cells feature motile cilia, microtubulebased surface actuators that sense and propel the extracellular fluidic environment (1-3). Whereas cilia and cilia-like structures that sort and capture bacteria or particles are common and well-characterized features of aquatic organisms (4-7), in terrestrial animals such as mammals, the internal location of ciliated surfaces has made them difficult to study. A central challenge in internal ciliated mucus membranes, such as those lining the fallopian tube, the Eustachian tube, and the respiratory system (8), is to reconcile the effective clearance of toxic molecules and undesirable microbes with selective engagement of beneficial symbionts. For example, on airway epithelia, the coordinated beat of motile cilia creates a horizontal flow across their tips (9-12), which clears mucus, microorganisms, and debris (Fig. 1A). Disruption of this mucociliary clearance can lead to chronic infection of the airways (13). However, this simple model is incomplete; ciliated airway epithelia not only serve a clearance function, but also provide a habitat and a gateway for coevolved symbionts that play an essential role in the development of the host...

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“…This volume transmission function remains significant in adulthood for the maintenance of brain homeostasis, and likely for brain repair. At the ventricular level, it benefits from an organized pattern of cilia modules whose beating controls substance distribution along the ependymal wall [43].…”

Section: The Cerebrospinal Fluid Compartments and Volume Transmissionmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

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The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

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Cilia-based flow network in the brain ventricles

Cited by 239 publications

References 24 publications

Prdm16 is required for the maintenance of neural stem cells in the postnatal forebrain and their differentiation into ependymal cells

Prdm16 is required for the maintenance of neural stem cells in the postnatal forebrain and their differentiation into ependymal cells

Motile cilia create fluid-mechanical microhabitats for the active recruitment of the host microbiome

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

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