scholarly journals Notch/Her12 signalling modulates, motile/immotile cilia ratio downstream of Foxj1a in zebrafish left-right organizer

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Barbara Tavares ◽  
Raquel Jacinto ◽  
Pedro Sampaio ◽  
Sara Pestana ◽  
Andreia Pinto ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Notch Signalling ◽  
Normal Fluid ◽  
Two Photon ◽  
Notch Intracellular Domain ◽  
Immotile Cilia ◽  
Flow Intensity ◽  
Dynein Arms ◽  
Motile Cilia ◽  
Necessary And Sufficient

Foxj1a is necessary and sufficient to specify motile cilia. Using transcriptional studies and slow-scan two-photon live imaging capable of identifying the number of motile and immotile cilia, we now established that the final number of motile cilia depends on Notch signalling (NS). We found that despite all left-right organizer (LRO) cells express foxj1a and the ciliary axonemes of these cells have dynein arms, some cilia remain immotile. We identified that this decision is taken early in development in the Kupffer’s Vesicle (KV) precursors the readout being her12 transcription. We demonstrate that overexpression of either her12 or Notch intracellular domain (NICD) increases the number of immotile cilia at the expense of motile cilia, and leads to an accumulation of immotile cilia at the anterior half of the KV. This disrupts the normal fluid flow intensity and pattern, with consequent impact on dand5 expression pattern and left-right (L-R) axis establishment.

scholarly journals Fluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires Bicc1-Ccr4 RNA degradation complex

2020 ◽  
Author(s):  
Katsura Minegishi ◽  
Benjamin Rothé ◽  
Kaoru R. Komatsu ◽  
Hiroki Ono ◽  
Yayoi Ikawa ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Mouse Embryo ◽  
Untranslated Region ◽  
Mrna Decay ◽  
Rna Binding ◽  
Flow Direction ◽  
Rna Degradation ◽  
Immotile Cilia ◽  
Necessary And Sufficient ◽  
Nucleotide Region

SUMMARYMolecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examined how the fluid flow induces Dand5 mRNA decay. We found that the 3’ untranslated region (3’-UTR) of Dand5 mRNA is necessary and sufficient for the left-sided decay and is responsive to the flow direction, loss of the cation channel Pkd2, and Ca2+. The 200-nucleotide proximal-most portion of the 3’-UTR, which is conserved among mammals, is essential for the asymmetric mRNA decay and binds Bicc1, an RNA binding protein specifically expressed at the node. Bicc1 preferentially recognizes GAC and GACR sequences in RNA, and these motifs are enriched in the 200-nucleotide region of the Dand5 3’-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required for Dand5 mRNA decay at the node. Our results thus suggest that leftward fluid flow induces binding of Bicc1 to the 3’-UTR of Dand5 mRNA in crown cells on the left side of the node, and that consequent recruitment of Ccr4-Not mediates mRNA degradation.

scholarly journals Fluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA degradation complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Katsura Minegishi ◽  
Benjamin Rothé ◽  
Kaoru R. Komatsu ◽  
Hiroki Ono ◽  
Yayoi Ikawa ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Mouse Embryo ◽  
Untranslated Region ◽  
Mrna Decay ◽  
Rna Binding ◽  
Specific Binding ◽  
Flow Direction ◽  
Rna Degradation ◽  
Immotile Cilia ◽  
Necessary And Sufficient

AbstractMolecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examined how the fluid flow induces Dand5 mRNA decay. We found that the first 200 nucleotides in the 3′ untranslated region (3′-UTR) of Dand5 mRNA are necessary and sufficient for the left-sided decay and to mediate the response of a 3′-UTR reporter transgene to Ca2+, the cation channel Pkd2, the RNA-binding protein Bicc1 and their regulation by the flow direction. We show that Bicc1 preferentially recognizes GACR and YGAC sequences, which can explain the specific binding to a conserved GACGUGAC motif located in the proximal Dand5 3′-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required for Dand5 mRNA decay at the node. These results suggest that Ca2+ currents induced by leftward fluid flow stimulate Bicc1 and Ccr4-Not to mediate Dand5 mRNA degradation specifically on the left side of the node.

scholarly journals Zebrafish Motile Cilia as a Model for Primary Ciliary Dyskinesia

2021 ◽  
Vol 22 (16) ◽  
pp. 8361
Author(s):  
Andreia L. Pinto ◽  
Margarida Rasteiro ◽  
Catarina Bota ◽  
Sara Pestana ◽  
Pedro Sampaio ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Primary Cilia ◽  
Electron Tomography ◽  
Model Organism ◽  
Autosomal Recessive Disorder ◽  
High Resolution Data ◽  
Immotile Cilia ◽  
Dynein Arms ◽  
Motile Cilia ◽  
Ciliary Dyskinesia

Zebrafish is a vertebrate teleost widely used in many areas of research. As embryos, they develop quickly and provide unique opportunities for research studies owing to their transparency for at least 48 h post fertilization. Zebrafish have many ciliated organs that include primary cilia as well as motile cilia. Using zebrafish as an animal model helps to better understand human diseases such as Primary Ciliary Dyskinesia (PCD), an autosomal recessive disorder that affects cilia motility, currently associated with more than 50 genes. The aim of this study was to validate zebrafish motile cilia, both in mono and multiciliated cells, as organelles for PCD research. For this purpose, we obtained systematic high-resolution data in both the olfactory pit (OP) and the left–right organizer (LRO), a superficial organ and a deep organ embedded in the tail of the embryo, respectively. For the analysis of their axonemal ciliary structure, we used conventional transmission electron microscopy (TEM) and electron tomography (ET). We characterised the wild-type OP cilia and showed, for the first time in zebrafish, the presence of motile cilia (9 + 2) in the periphery of the pit and the presence of immotile cilia (still 9 + 2), with absent outer dynein arms, in the centre of the pit. In addition, we reported that a central pair of microtubules in the LRO motile cilia is common in zebrafish, contrary to mouse embryos, but it is not observed in all LRO cilia from the same embryo. We further showed that the outer dynein arms of the microtubular doublet of both the OP and LRO cilia are structurally similar in dimensions to the human respiratory cilia at the resolution of TEM and ET. We conclude that zebrafish is a good model organism for PCD research but investigators need to be aware of the specific physical differences to correctly interpret their results.

Bronchial stereocilia in the immotile cilia syndrome: A case report

1984 ◽  
Vol 42 ◽  
pp. 52-53
Author(s):  
George Price ◽  
Lizardo Cerezo
Keyword(s):  
Surface Modifications ◽  
Respiratory Epithelium ◽  
Immotile Cilia ◽  
Kartagener's Syndrome ◽  
Membrane Blebs ◽  
Radial Spokes ◽  
Males And Females ◽  
Dynein Arms ◽  
Ultrastructural Finding ◽  
Ultrastructural Findings

Ultrastructural defects of ciliary structure have been known to cause recurrent sino-respiratory infection concurrent with Kartagener's syndrome. (1,2,3) These defects are also known to cause infertility in both males and females. (4) Overall, the defects are defined as the Immotile, or Dyskinetic Cilia Syndrome (DCS). Several ultrastructural findings have been described, including decreased number of cilia, multidirection orientation, fused and compound cilia, membrane blebs, excess matrix in the axoneme, missing outer tubular doublets, translocated doublets, defective radial spokes and dynein arms. A rare but noteworthy ultrastructural finding in DCS is the predominance of microvilli-like structures on the luminal surface of the respiratory epithelium. (5,6) These permanent surface modifications of the apical respiratory epithelium no longer resemble cilia but reflect the ultrastructure of stereocilia, similar to that found in the epidydimal epithelium. Like microvilli, stereocilia are devoid of microtubular ultrastructure in comparison with true cilia.

Normal Ciliary Ultrastructure in Children with Kartagener's Syndrome

1980 ◽  
Vol 89 (1) ◽  
pp. 81-83 ◽  
Author(s):  
Fred S. Herzon ◽  
Shirley Murphy
Keyword(s):  
Immotile Cilia Syndrome ◽  
Normal Limits ◽  
Immotile Cilia ◽  
Kartagener's Syndrome ◽  
Radial Spokes ◽  
Dynein Arms ◽  
Ciliary Ultrastructure

Kartagener's syndrome has been found to be associated with the immotile cilia syndrome (lack of dynein arms and defective radial spokes in cilia). The ultrastructure of cilia of a child with Kartagener's syndrome was examined and found to be within normal limits. The implications of this are discussed.

scholarly journals Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis

2009 ◽  
Vol 15 (1) ◽  
pp. 175-185 ◽  
Author(s):  
Rodrigo Hernández Vera ◽  
Elsa Genové ◽  
Lery Alvarez ◽  
Salvador Borrós ◽  
Roger Kamm ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Interstitial Fluid ◽  
Interstitial Fluid Flow ◽  
Capillary Morphogenesis ◽  
Cell Clusters ◽  
Flow Intensity

Cilia Not Only Move, but also Have Taste!

2010 ◽  
Vol 18 (2) ◽  
pp. 6-8
Author(s):  
Stephen W. Carmichael
Keyword(s):  
Molecular Machines ◽  
Sensory Function ◽  
Mechanical Activity ◽  
Sensory Receptors ◽  
Pulmonary Infections ◽  
Immotile Cilia ◽  
Specific Direction ◽  
Motile Cilia ◽  
First Time ◽  
Sensory Functions

Motile cilia are organelles that contain amazing molecular machines that bend each cilium in a rhythmic and coordinated movement. This allows a liquid film, perhaps with particles embedded within, to move in a specific direction. The classic example is the cilia of the respiratory passages that move a layer of debris-carrying mucus out of the lungs. When this mechanism is not working properly, recurrent pulmonary infections result. The classic example of this is immotile cilia syndrome that results in chronic bronchitis and related problems. However, no sensory function has been assigned to these classic motile cilia until now (although nodal cilia have both mechanical activity and sensory functions). Alok Shah, Yehuda Ben-Shahar, Thomas Moninger, Joel Kline, and Michael Welsh have demonstrated sensory receptors on motile cilia for the first time.

scholarly journals A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice

2020 ◽  
Vol 13 (10) ◽  
pp. dmm045344
Author(s):  
Zakia Abdelhamed ◽  
Marshall Lukacs ◽  
Sandra Cindric ◽  
Heymut Omran ◽  
Rolf W. Stottmann
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Primary Ciliary Dyskinesia ◽  
Human Condition ◽  
Central Pair ◽  
Cerebrospinal Fluid Flow ◽  
Hypomorphic Allele ◽  
Motile Cilia ◽  
The Brain ◽  
Ciliary Dyskinesia

ABSTRACTPrimary ciliary dyskinesia (PCD) is a human condition of dysfunctional motile cilia characterized by recurrent lung infection, infertility, organ laterality defects and partially penetrant hydrocephalus. We recovered a mouse mutant from a forward genetic screen that developed many of the hallmark phenotypes of PCD. Whole-exome sequencing identified this primary ciliary dyskinesia only (Pcdo) allele to be a nonsense mutation (c.5236A>T) in the Spag17 coding sequence creating a premature stop codon (K1746*). The Pcdo variant abolished several isoforms of SPAG17 in the Pcdo mutant testis but not in the brain. Our data indicate differential requirements for SPAG17 in different types of motile cilia. SPAG17 is essential for proper development of the sperm flagellum and is required for either development or stability of the C1 microtubule structure within the central pair apparatus of the respiratory motile cilia, but not the brain ependymal cilia. We identified changes in ependymal ciliary beating frequency, but these did not appear to alter lateral ventricle cerebrospinal fluid flow. Aqueductal stenosis resulted in significantly slower and abnormally directed cerebrospinal fluid flow, and we suggest that this is the root cause of the hydrocephalus. The Spag17Pcdo homozygous mutant mice are generally viable to adulthood but have a significantly shortened lifespan, with chronic morbidity. Our data indicate that the c.5236A>T Pcdo variant is a hypomorphic allele of Spag17 that causes phenotypes related to motile, but not primary, cilia. Spag17Pcdo is a useful new model for elucidating the molecular mechanisms underlying central pair PCD pathogenesis in the mouse.This article has an associated First Person interview with the first author of the paper.

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