Strain-specific differences in brain gene expression in a hydrocephalic mouse model with motile cilia dysfunction
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PROVIDER: PRJNA450525 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of strain-specific differences in gene expression in brains from a hydrocephalic mouse model of primary ciliary dyskinesia. The results identify genes that are differentially expressed between C57BL6/J and 129S6/SvEvTac brains. These genes encode proteins that function in a variety of cellular processes and include some that are relevant to hydrocephalus and cilia function, providing insight into the mechanisms underlying susceptibility to hydrocephalus.
2018-09-06 | GSE113233 | GEO
Project description:Progressive ventricular enlargement is one of the most reproducible and recognizable structural abnormalities in schizophrenia, and is associated with more severe symptoms and poorer clinical outcome. The mechanisms of ventricular enlargement in schizophrenia is unknown. We identified that progressive ventricular enlargement is associated with deceleration of motile cilia beating in ependymal cells lining ventricular walls in murine models of schizophrenia-associated 22q11 deletion syndrome (22q11DS). The cilia beating deficit is caused by an aberrant elevation of Drd1, which is highly enriched in the motile cilia. Haploinsufficiency of the microRNA-processing gene Dgcr8 is responsible for the Drd1 elevation in ependymal cells of 22q11DS mice, and is mediated by reduction of Drd1-targeting microRNAs miR-674-3p and miR-382-3p. Replenishing miR-674-3p or miR-382-3p in 22q11DS mice rescued the motile cilia beating abnormalities and normalized the ventricular size. Knockdown of these microRNA mimicked cilia beating and ventricular deficits. Ventricular enlargement was also caused by Crispr/cas9-mediated deletion of the Drd1 seed site for miR-674-3p/miR-382-3p. This suggests that Dgcr8-miR-674-3p/miR-382-3p-Drd1–dependent disruption of cilia motility in ependymal cells is a pathogenic event underlying schizophrenia-associated ventricular enlargement.
2019-12-07 | GSE123560 | GEO
Project description:ARL13B is a small regulatory GTPase that controls ciliary membrane composition in both motile cilia and non-motile primary cilia. In this study, we investigated the role of ARL13B in the efferent ductules, tubules of the male reproductive tract essential to male fertility in which primary and motile cilia co-exist. We used a genetically engineered mouse model to deleteArl13bin efferent ductule epithelial cells, resulting in compromised primary and motile cilia architecture and functions. This deletion led to disturbances in reabsorptive/secretory processes and triggered an inflammatory response. The observed male reproductive phenotype showed significant variability linked to partial infertility, highlighting the importance of ARL13B in maintaining a proper physiological balance in these small ducts. These results emphasize the dual role of both motile and primary cilia functions in regulating efferent duct homeostasis, offering deeper insights into how cilia related diseases affect the male reproductive system.
2024-09-30 | GSE256400 | GEO
Project description:The brain uses a specialized system to transport cerebrospinal fluid (CSF) that is essential for brain homeostasis. This system consists of interconnected ventricles lined by ependymal cells, which generate a directional flow upon beating of their motile cilia. Notably, motile cilia act jointly with other physiological factors, including active CSF secretion and cardiac pressure gradients, to regulate CSF dynamics. The content of CSF and its movement in brain ventricles are thought to be important for brain physiology. Yet, the link between cilia mediated CSF flow and brain function is poorly understood. In this study, we specifically addressed the role of motile cilia-mediated CSF flow on brain development and physiology using zebrafish larvae as a model system. By analyzing mutant animals with paralyzed cilia, we identified that loss of cilia motility did not alter progenitor proliferation, overall brain morphology, or baseline neural activity. Instead, we identified that loss of ciliary motility led to randomization of brain asymmetry. We also observed altered neuronal responses to photic stimulation, especially in the optic tectum and hindbrain. Since astroglia contact CSF at the ventricular walls and are essential for regulating neuronal activity, we next investigated astroglial activity in motile cilia mutants. Our analyses revealed a striking reduction in astroglial calcium signals both during spontaneous and light-evoked activity. Altogether, our findings highlight a novel role of motile cilia-mediated flow in regulating brain physiology through modulation of neural and astroglial networks.
2024-11-22 | GSE254006 | GEO
Project description:Congenital hydrocephalus results from cerebrospinal fluid accumulation in the ventricles of the brain and causes severe neurological damage, but the underlying causes are not well understood. It is associated with several syndromes, including primary ciliary dyskinesia (PCD), which is caused by dysfunction of motile cilia. We previously demonstrated that mouse models of PCD lacking ciliary proteins CFAP221, CFAP54 and SPEF2 all have hydrocephalus with a strain-dependent severity. While morphological defects are more severe on the C57BL/6J (B6) background than 129S6/SvEvTac (129), cerebrospinal fluid flow is perturbed on both backgrounds, suggesting that abnormal cilia-driven flow is not the only factor underlying the hydrocephalus phenotype. Here, we performed a microarray analysis on brains from wild type and nm1054 mice lacking CFAP221 on the B6 and 129 backgrounds. Expression differences were observed for a number of genes that cluster into distinct groups based on expression pattern and biological function, many of them implicated in cellular and biochemical processes essential for proper brain development. These include genes known to be functionally relevant to congenital hydrocephalus, as well as formation and function of both motile and sensory cilia. Identification of these genes provides important clues to mechanisms underlying congenital hydrocephalus severity.
| S-EPMC6127338 | biostudies-literature
Project description:Eukaryotic cilia and flagella are essential for cell motility and sensory functions. Their biogenesis and maintenance rely on the intraflagellar transport (IFT). Several cargo adapters have been identified to aid IFT cargo transport, but how ciliary cargos are discharged from IFT remains largely unknown. During our explorations of small GTPases ARL13 and ARL3 in Trypanosoma brucei, we found that ODA16, a known IFT cargo adapter found exclusively in motile cilia, is a specific effector of ARL3. To investigate how TbARL3A and TbARL3C regulate TbODA16, we performed proximity-dependent biotin identification (BioID) and mass spectrometry analyses for TbODA16 in the presence or absence of TbARL3A and TbARL3C.
2024-09-05 | PXD053760 | Pride
Project description:Two 75-cm2 flasks of ependymal cells derived from ten E18.5 Wdr47+/+ or Wdr47-/- embryos at the day 10 post serum starvation were harvested and motile cilia were purified for quantitative label-free proteomic analysis.
2021-09-07 | PXD028219 |
Project description:Analysis of epithelial explants injected with the intracellular domain of Notch (ICD) to block the formation of multi-ciliate cells, either alone or along with FoxJ1. FoxJ1 misexpression leads to the induction fo ectopic cilia in Xenopus laevis epithelia. Results show which genes are affected by FoxJ1 during the induction of ectopic cilia. Ciliated cells that produce a leftward fluid flow have been proposed to mediate left-right patterning in many vertebrate embryos. These cilia combine features of primary sensory and motile cilia, but how such cilia are specified is unknown. We address this issue by analyzing the Xenopus and Zebrafish homologs of FoxJ1, a forkhead transcription factor necessary for ciliogenesis in multi-ciliate cells of the mouse. We show that the cilia that underlie left-right patterning on the Xenopus gastrocoel roof plate (GRP) and Zebrafish Kupffer’s vesicle (KV) are severely shortened or fail to form in FoxJ1 morphants. We also show that misexpressing XFoxJ1 is sufficient to induce ectopic GRP-like cilia formation in frog embryos. Microarray analysis indicates that XFoxJ1 induces the formation of cilia by upregulating the expression of motile cilia genes. These results indicate that FoxJ1 is a critical determinant in specifying cilia used in left-right patterning. Keywords: Cilia Induction
2008-09-15 | GSE12613 | GEO
Project description:Schizophrenia-related microdeletion causes progressive brain ventricle enlargement through microRNA-dependent deceleration of motile cilia beating
| PRJNA509221 | ENA
Project description:Two 75-cm2 flasks of ependymal cells derived from ten E18.5 C57BL/6J mouse embryos at the day 10 post serum starvation were harvested and motile cilia were collected for mass spectrometry analysis.
2021-10-18 | PXD029174 |