Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of the FTO-FOXJ1 axis as a conserved regulatory module of embryonic and homeostatic motile ciliogenesis

ABSTRACT: Adenosine N6-methylation (m6A) is one of the most pervasive mRNA modifications, and yet the physiological significance of m6A removal (demethylation) remains elusive. Here we report the m6A demethylase FTO functions as a conserved regulator of motile ciliogenesis. Mechanistically, FTO demethylates and thereby stabilizes the mRNA encoding the master ciliary transcription factor FOXJ1. Depletion of Fto in Xenopus laevis embryos caused widespread motile cilia defects, and Foxj1 was identified as one of the major phenocritical targets. In primary human airway epithelium, FTO depletion also led to FOXJ1 mRNA destabilization and a severe loss of ciliated cells with an increase of neighboring goblet cells. Consistently, Fto knockout mice showed strong asthma-like phenotypes upon allergen challenge owing to defective ciliated cells in the airway epithelium. Altogether, our study reveals a conserved role of the FTO-FOXJ1 axis in embryonic and homeostatic motile ciliogenesis.

ORGANISM(S): Xenopus laevis

PROVIDER: GSE167139 | GEO | 2021/02/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Identification of FOXJ1 effectors during ciliogenesis in the fetal respiratory epithelium and embryonic left-right organizer of the mouse - Noto screen

Project description:Formation of motile cilia in vertebrate embryos is essential for proper development and tissue function. Key regulators of motile ciliogenesis are the transcription factors FOXJ1 and NOTO, which are conserved throughout vertebrates. Downstream target genes of FOXJ1 have been identified in a variety of species, organs and cultured cell lines; in murine embryonic and foetal tissues, however, FOXJ1 and NOTO effectors have not been comprehensively analysed and our knowledge of the downstream genetic programme driving motile ciliogenesis in the mammalian lung and ventral node is fragmentary. We compared genome-wide expression profiles of undifferentiated E14.5 vs. abundantly ciliated E18.5 micro-dissected airway epithelia as well as Foxj1+ vs. Foxj1-deficient foetal (E16.5) lungs of the mouse using microarray hybridisation. 326 genes deregulated in both screens are candidates for FOXJ1-dependent, ciliogenesis-associated factors at the endogenous onset of motile ciliogenesis in the lung, including 123 genes that have not been linked to ciliogenesis before; 46% of these novel factors lack known homologues outside mammals. Microarray screening of Noto+ vs. Noto null early headfold embryos (E7.75) identified 59 of the lung candidates as NOTO/FOXJ1-dependent factors in the embryonic left-right organiser that carries a different subtype of motile cilia. For several uncharacterised factors from this small overlap – including 1700012B09Rik, 1700026L06Rik and Fam183b – we provide extended experimental evidence for a ciliary function.

2017-09-18 | GSE89583 | GEO

Identification of FOXJ1 effectors during ciliogenesis in the fetal respiratory epithelium and embryonic left-right organizer of the mouse - IMCD3 screen

2017-09-18 | GSE89584 | GEO

Identification of FOXJ1 effectors during ciliogenesis in the fetal respiratory epithelium and embryonic left-right organizer of the mouse - Lung subscreen B

2017-09-18 | GSE89582 | GEO

Identification of FOXJ1 effectors during ciliogenesis in the fetal respiratory epithelium and embryonic left-right organizer of the mouse - Lung subscreen A

2017-09-18 | GSE89581 | GEO

Foxj1 controls olfactory ciliogenesis and differentiation program of the olfactory sensory neurons

Project description:Olfaction plays important roles in food and mate choice, and also in the avoidance of predators, making it a vital sensory modality for preservation and reproduction. In the vertebrates, olfactory receptors are thought to localise on multiple cilia elaborated on the dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause loss of the sense of smell, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a fork head-domain containing transcription factor traditionally linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium formation. In keeping with the immotile nature of the olfactory cilia, we observed that ciliary motility genes that are the targets of Foxj1 in motile ciliated cells, are repressed in the OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the differentiation of the OSNs by regulating their cell type-specific gene expression, such as that of olfactory marker protein (omp) involved in odour-evoked signal transduction. In line with these requirements, response to bile acid, an odour detected by OMP-positive OSNs, was significantly diminished in the foxj1 mutant zebrafish. Taken together, our findings establish how the canonical Foxj1-mediated motile ciliogenic transcriptional program has been repurposed for the biogenesis of the immotile olfactory cilia and for the development of the OSNs themselves.

2023-12-04 | GSE232397 | GEO

Effect of FoxJ1 on expression of cilia genes

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

Transcription profiling of Xenopus epithelial explants injected with the intracellular domain of Notch (ICD) to block the formation of multi-ciliate cells, either alone or along with FoxJ1

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 Kupfferâs 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. Experiment Overall Design: 2-cell stage Xenopus embryos were injected with synthetic mRNA encoding ICD alone or along with FoxJ1. At stage 9/10 the presumptive ectoderm was cut off the embryo and cultured on a fibronectin coated coverslip. At stage 22 RNA was harvested from explants and used as the starting material for arrays.

2008-10-25 | E-GEOD-12613 | biostudies-arrayexpress

MicroRNA signature during the time course of regeneration of the human airway mucociliary epithelium

Project description:The regeneration of the airway mucociliary epithelium involves several sequential events including migration, proliferation, polarization and final differentiation (i.e ciliogenesis). The airway mucociliary epithelium is consituted of three main cell types : ciliated cells, secretory cells and basal cells. We used microRNA microrrays to investigate the signature of microRNA during the four step of regeneration of the airway epithelium. Four time points (ALI-D0, ALI-D7, ALI-D14, ALI-D21) of regeneration of the airway epithelium for 3 donors.

2011-06-06 | E-GEOD-22141 | biostudies-arrayexpress

miRNAs high throughput sequencing profiling of regenerating human airway epithelial cells

2011-06-06 | E-GEOD-22144 | biostudies-arrayexpress