XB-ART-59035
Int J Mol Sci
2022 Feb 03;233:. doi: 10.3390/ijms23031749.
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PCD Genes-From Patients to Model Organisms and Back to Humans.
Niziolek M
,
Bicka M
,
Osinka A
,
Samsel Z
,
Sekretarska J
,
Poprzeczko M
,
Bazan R
,
Fabczak H
,
Joachimiak E
,
Wloga D
.
???displayArticle.abstract???
Primary ciliary dyskinesia (PCD) is a hereditary genetic disorder caused by the lack of motile cilia or the assembxly of dysfunctional ones. This rare human disease affects 1 out of 10,000-20,000 individuals and is caused by mutations in at least 50 genes. The past twenty years brought significant progress in the identification of PCD-causative genes and in our understanding of the connections between causative mutations and ciliary defects observed in affected individuals. These scientific advances have been achieved, among others, due to the extensive motile cilia-related research conducted using several model organisms, ranging from protists to mammals. These are unicellular organisms such as the green alga Chlamydomonas, the parasitic protist Trypanosoma, and free-living ciliates, Tetrahymena and Paramecium, the invertebrate Schmidtea, and vertebrates such as zebrafish, Xenopus, and mouse. Establishing such evolutionarily distant experimental models with different levels of cell or body complexity was possible because both basic motile cilia ultrastructure and protein composition are highly conserved throughout evolution. Here, we characterize model organisms commonly used to study PCD-related genes, highlight their pros and cons, and summarize experimental data collected using these models.
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OPUS15 2018/29/B/NZ3/02443 National Science Centre, Poland, OPUS13 2017/25/B/NZ3/01609 National Science Centre, Poland
Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: lhx6 mia pcbd1
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Figure 1. Schematic representation of the motile cilium ultrastructure. Cilium cross-section (on the left, view from the side of the basal body) and a 96 nm-long fragment of the outer doublet with docked ciliary complexes (called the 96 nm axonemal unit, on the right). Each axonemal unit contains four outer dynein arms (ODAs, in violet); seven inner dynein arms: heterodimeric (α, β) IDAf/I1 and single-headed IDA a, b, c, e, g, and d, (dark blue); the nexinâdynein regulatory complex (N-DRC, red) that coordinates the activity of ciliary complexes within the axonemal unit and connects two adjacent outer doublets; and three radial spokes (RS, cyan) that transiently interact with central apparatus projections via their heads, while the base of the stalk comes in contact with two different IDAs [32]. The main complexes are accompanied by several minor complexes that modulate and/or connect large ciliary complexes (e.g., tether/tether head complex (T/TH, orange [33]) positioned near IDA f/I1, CSC complex positioned at the bases of RS2 and RS3 (location indicated by an arrow) [34,35], MIA complex (green) connecting N-DRC and IDA f/I1 [36], and CCDC113/CCDC96 linker (yellow) connecting RS3, N-DRC, and IDAg [37]. |
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Figure 2. A schematic representation of the nonâvertebrate PCD model organisms, the unicellular (a) Green alga Chlamydomonas reinhardtii; (b) Parasitic protist, Trypanosoma brucei (bloodstream-form) and two freeâliving ciliates, (c) Paramecium tetraurelia and (d) Tetrahymena thermophila as well as the multicellular (e) Freshwater planarian flatworm, Schmidtea mediterranea, with an enlarged fragment showing the multiciliated cells (MCCs) of the ventral epidermis. Nucleus (cyan), motile 9 Ã 2 + 2 cilia/flagella (green). |
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Figure 3. A schematic representation of the larval and adult forms of vertebrate PCD models, (a) zebrafish and (b) Xenopus. The adult animals reach the following sizes: zebrafish ~3.5 cm; X. laevis, males between 4.5 and 9.8 cm, females from 5.7 to 14.7 cm; X. tropicalis, males between 3.2 and 3.9 cm, females between 4.8 and 5.5 cm (https://zfin.org/zf_info/zfbook/stages/ accessed on 30 December 2021 [239], http://www.xenbase.org accessed on 30 December 2021 [240]). Nuclei (cyan), motile 9 Ã 2 + 2 cilia (green), motile 9 Ã 2 + 0 central canal cilia (navy blue), immotile cilia (red), motile cilia in gastrocoel roof plate of unknown microtubule configuration (grey). |
References [+] :
Abdelhamed,
A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.
2018, Pubmed
Abdelhamed, A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice. 2018, Pubmed
Afzelius, Structure and function of neutrophil leukocytes from patients with the immotile-cilia syndrome. 1980, Pubmed
Ahmed, ODA16p, a Chlamydomonas flagellar protein needed for dynein assembly. 2005, Pubmed
Ahmed, ODA16 aids axonemal outer row dynein assembly through an interaction with the intraflagellar transport machinery. 2008, Pubmed
Ahmed, Generation of the induced pluripotent stem cell line UHOMi001-A from a patient with mutations in CCDC40 gene causing Primary Ciliary Dyskinesia (PCD). 2018, Pubmed
Amirav, Systematic Analysis of CCNO Variants in a Defined Population: Implications for Clinical Phenotype and Differential Diagnosis. 2016, Pubmed , Xenbase
An, FAZ27 cooperates with FLAM3 and ClpGM6 to maintain cell morphology in Trypanosoma brucei. 2020, Pubmed
Ansari, Micro-anatomical and functional assessment of ciliated epithelium in mouse trachea using optical coherence phase microscopy. 2015, Pubmed
Antony, Ciliary Dyneins and Dynein Related Ciliopathies. 2021, Pubmed
Anvarian, Cellular signalling by primary cilia in development, organ function and disease. 2019, Pubmed
Aprea, Defects in the cytoplasmic assembly of axonemal dynein arms cause morphological abnormalities and dysmotility in sperm cells leading to male infertility. 2021, Pubmed
Aprea, Motility of efferent duct cilia aids passage of sperm cells through the male reproductive system. 2021, Pubmed
Aubusson-Fleury, Ciliary heterogeneity within a single cell: the Paramecium model. 2015, Pubmed
Auer, CRISPR/Cas9 and TALEN-mediated knock-in approaches in zebrafish. 2014, Pubmed
Austin-Tse, Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia. 2013, Pubmed
Azimzadeh, Basal bodies across eukaryotes series: basal bodies in the freshwater planarian Schmidtea mediterranea. 2016, Pubmed
Bachmaier, Culturing and Transfection of Pleomorphic Trypanosoma brucei. 2020, Pubmed
Barber, Three-dimensional structure of the radial spokes reveals heterogeneity and interactions with dyneins in Chlamydomonas flagella. 2012, Pubmed
Baron, Stuck in reverse: loss of LC1 in Trypanosoma brucei disrupts outer dynein arms and leads to reverse flagellar beat and backward movement. 2007, Pubmed
Basquin, The planarian Schmidtea mediterranea as a model for studying motile cilia and multiciliated cells. 2015, Pubmed
Bazan, Ccdc113/Ccdc96 complex, a novel regulator of ciliary beating that connects radial spoke 3 to dynein g and the nexin link. 2021, Pubmed
Becker-Heck, The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. 2011, Pubmed
Bertiaux, Intraflagellar transport during assembly of flagella of different length in Trypanosoma brucei isolated from tsetse flies. 2020, Pubmed
Blitz, Control of zygotic genome activation in Xenopus. 2021, Pubmed , Xenbase
Blum, Xenopus: An Undervalued Model Organism to Study and Model Human Genetic Disease. 2018, Pubmed , Xenbase
Blum, Xenopus, an ideal model system to study vertebrate left-right asymmetry. 2009, Pubmed , Xenbase
Bonnefoy, Biallelic Mutations in LRRC56, Encoding a Protein Associated with Intraflagellar Transport, Cause Mucociliary Clearance and Laterality Defects. 2018, Pubmed
Boskovski, The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. 2013, Pubmed , Xenbase
Bowes, Xenbase: a Xenopus biology and genomics resource. 2008, Pubmed , Xenbase
Branche, Conserved and specific functions of axoneme components in trypanosome motility. 2006, Pubmed
Breeze, The cells of the pulmonary airways. 1977, Pubmed
Brennan, Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia. 2021, Pubmed
Brndiarova, Changes of Motile Ciliary Phenotype in Patients with Primary Ciliopathies. 2021, Pubmed
Brooks, In vivo investigation of cilia structure and function using Xenopus. 2015, Pubmed , Xenbase
Brooks, Multiciliated cells. 2014, Pubmed
Bruni, A scanning electron microscopic study of the ependymal surface of the third ventricle of the rabbit, rat, mouse and human brain. 1972, Pubmed
Burkard, Highly efficient stable transformation of bloodstream forms of Trypanosoma brucei. 2007, Pubmed
Burnicka-Turek, Cilia gene mutations cause atrioventricular septal defects by multiple mechanisms. 2016, Pubmed
Bustamante-Marin, Cilia and Mucociliary Clearance. 2017, Pubmed
Bustamante-Marin, Mutation of CFAP57, a protein required for the asymmetric targeting of a subset of inner dynein arms in Chlamydomonas, causes primary ciliary dyskinesia. 2020, Pubmed
Bustamante-Marin, Lack of GAS2L2 Causes PCD by Impairing Cilia Orientation and Mucociliary Clearance. 2019, Pubmed , Xenbase
Cao, Intraflagellar transport proteins are essential for cilia formation and for planar cell polarity. 2010, Pubmed
Cao, Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells-overview and perspectives. 2021, Pubmed
Carradec, Primary and secondary siRNA synthesis triggered by RNAs from food bacteria in the ciliate Paramecium tetraurelia. 2015, Pubmed
Carvalho-Santos, Evolution: Tracing the origins of centrioles, cilia, and flagella. 2011, Pubmed
Castleman, Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. 2009, Pubmed
Chalker, Transformation and strain engineering of Tetrahymena. 2012, Pubmed
Cheong, A null allele of Dnaaf2 displays embryonic lethality and mimics human ciliary dyskinesia. 2019, Pubmed
Cho, A nonsense variant in NME5 causes human primary ciliary dyskinesia with radial spoke defects. 2020, Pubmed
Chung, RFX2 is broadly required for ciliogenesis during vertebrate development. 2012, Pubmed , Xenbase
Cindrić, SPEF2- and HYDIN-Mutant Cilia Lack the Central Pair-associated Protein SPEF2, Aiding Primary Ciliary Dyskinesia Diagnostics. 2020, Pubmed
Cockx, The Antimicrobial Activity of Peripheral Blood Neutrophils Is Altered in Patients with Primary Ciliary Dyskinesia. 2021, Pubmed
Cockx, Monocytes from patients with Primary Ciliary Dyskinesia show enhanced inflammatory properties and produce higher levels of pro-inflammatory cytokines. 2017, Pubmed
Colantonio, The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear. 2009, Pubmed
Coles, A Revised Protocol for Culture of Airway Epithelial Cells as a Diagnostic Tool for Primary Ciliary Dyskinesia. 2020, Pubmed
Coutton, Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human. 2018, Pubmed
Dahlmann, Generation of two hiPSC lines (MHHi016-A, MHHi016-B) from a primary ciliary dyskinesia patient carrying a homozygous 5 bp duplication (c.248_252dup (p.Gly85Cysfs*11)) in exon 1 of the CCNO gene. 2020, Pubmed
Dave, Manipulating ciliary protein-encoding genes in Tetrahymena thermophila. 2009, Pubmed
Dawe, The hydrocephalus inducing gene product, Hydin, positions axonemal central pair microtubules. 2007, Pubmed
de Jong, Ciliogenesis in human bronchial epithelial cells cultured at the air-liquid interface. 1994, Pubmed
Delgehyr, Ependymal cell differentiation, from monociliated to multiciliated cells. 2015, Pubmed
Desai, Chlamydomonas axonemal dynein assembly locus ODA8 encodes a conserved flagellar protein needed for cytoplasmic maturation of outer dynein arm complexes. 2015, Pubmed
De Sousa, Maintenance of Schmidtea mediterranea in the Laboratory. 2018, Pubmed
Dhokane, CRISPR based targeted genome editing of Chlamydomonas reinhardtii using programmed Cas9-gRNA ribonucleoprotein. 2020, Pubmed
DiPetrillo, Pcdp1 is a central apparatus protein that binds Ca(2+)-calmodulin and regulates ciliary motility. 2010, Pubmed
Dixon, Secondary defects detected by transmission electron microscopy in primary ciliary dyskinesia diagnostics. 2017, Pubmed
Dong, Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse. 2018, Pubmed
Donnelley, Tracking extended mucociliary transport activity of individual deposited particles: longitudinal synchrotron X-ray imaging in live mice. 2014, Pubmed
Dougherty, CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module. 2020, Pubmed
Dougherty, DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes. 2016, Pubmed
Drick, Generation of two human induced pluripotent stem cell lines (MHHi017-A, MHHi017-B) from a patient with primary ciliary dyskinesia carrying a homozygous mutation (c.7915C > T [p.Arg2639*]) in the DNAH5 gene. 2020, Pubmed
Duquesnoy, Loss-of-function mutations in the human ortholog of Chlamydomonas reinhardtii ODA7 disrupt dynein arm assembly and cause primary ciliary dyskinesia. 2009, Pubmed
Dymek, The CSC is required for complete radial spoke assembly and wild-type ciliary motility. 2011, Pubmed
Eenjes, A novel method for expansion and differentiation of mouse tracheal epithelial cells in culture. 2018, Pubmed
Ermakov, Mouse mutagenesis identifies novel roles for left-right patterning genes in pulmonary, craniofacial, ocular, and limb development. 2009, Pubmed
Evron, Growth Arrest Specific 8 (Gas8) and G protein-coupled receptor kinase 2 (GRK2) cooperate in the control of Smoothened signaling. 2011, Pubmed
Fabczak, Role of the Novel Hsp90 Co-Chaperones in Dynein Arms' Preassembly. 2019, Pubmed
Falk, Specialized Cilia in Mammalian Sensory Systems. 2015, Pubmed
Falkenberg, Ccdc103 promotes myeloid cell proliferation and migration independent of motile cilia. 2021, Pubmed
Fassad, C11orf70 Mutations Disrupting the Intraflagellar Transport-Dependent Assembly of Multiple Axonemal Dyneins Cause Primary Ciliary Dyskinesia. 2018, Pubmed
Fassad, Mutations in Outer Dynein Arm Heavy Chain DNAH9 Cause Motile Cilia Defects and Situs Inversus. 2018, Pubmed
Finn, Strain-dependent brain defects in mouse models of primary ciliary dyskinesia with mutations in Pcdp1 and Spef2. 2014, Pubmed
Firth, Generation of multiciliated cells in functional airway epithelia from human induced pluripotent stem cells. 2014, Pubmed
Fliegauf, Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia. 2005, Pubmed
FLOCK, THE ULTRASTRUCTURE OF THE KINOCILIUM OF THE SENSORY CELLS IN THE INNER EAR AND LATERAL LINE ORGANS. 1965, Pubmed
Focșa, Clinical and genetic heterogeneity of primary ciliopathies (Review). 2021, Pubmed
Ford, A Cell/Cilia Cycle Biosensor for Single-Cell Kinetics Reveals Persistence of Cilia after G1/S Transition Is a General Property in Cells and Mice. 2018, Pubmed
Fox, Quantitative description of fluid flows produced by left-right cilia in zebrafish. 2015, Pubmed
Freshour, Chlamydomonas flagellar outer row dynein assembly protein ODA7 interacts with both outer row and I1 inner row dyneins. 2007, Pubmed
Fu, The I1 dynein-associated tether and tether head complex is a conserved regulator of ciliary motility. 2018, Pubmed
Fu, Structural organization of the C1a-e-c supercomplex within the ciliary central apparatus. 2019, Pubmed
Gabrion, Ependymal and choroidal cells in culture: characterization and functional differentiation. 1998, Pubmed
Gaertig, Discovery and functional evaluation of ciliary proteins in Tetrahymena thermophila. 2013, Pubmed
Galvani, RNA interference by feeding in Paramecium. 2002, Pubmed
Gama Sosa, Modeling human neurodegenerative diseases in transgenic systems. 2012, Pubmed
Gao, Oda16/Wdr69 is essential for axonemal dynein assembly and ciliary motility during zebrafish embryogenesis. 2010, Pubmed
Gogendeau, MKS-NPHP module proteins control ciliary shedding at the transition zone. 2020, Pubmed
Gonçalves, The Ciliary Transition Zone: Finding the Pieces and Assembling the Gate. 2017, Pubmed
Gotesman, Using a Hand-Held Gene Gun for Genetic Transformation of Tetrahymena thermophila. 2022, Pubmed
Grondona, A simple method to obtain pure cultures of multiciliated ependymal cells from adult rodents. 2013, Pubmed
Grubb, Reduced mucociliary clearance in old mice is associated with a decrease in Muc5b mucin. 2016, Pubmed
Guzmán-Zapata, Efficient Editing of the Nuclear APT Reporter Gene in Chlamydomonas reinhardtii via Expression of a CRISPR-Cas9 Module. 2019, Pubmed
Ha, Mutations in Dnaaf1 and Lrrc48 Cause Hydrocephalus, Laterality Defects, and Sinusitis in Mice. 2016, Pubmed
Hagenlocher, Ciliogenesis and cerebrospinal fluid flow in the developing Xenopus brain are regulated by foxj1. 2013, Pubmed , Xenbase
Harris, CHLAMYDOMONAS AS A MODEL ORGANISM. 2001, Pubmed
Hawkins, Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells. 2021, Pubmed
Hazime, STORM imaging reveals the spatial arrangement of transition zone components and IFT particles at the ciliary base in Tetrahymena. 2021, Pubmed
He, Novel homozygous CFAP69 mutations in humans and mice cause severe asthenoteratospermia with multiple morphological abnormalities of the sperm flagella. 2019, Pubmed
Heasman, Morpholino oligos: making sense of antisense? 2002, Pubmed , Xenbase
Heuser, The dynein regulatory complex is the nexin link and a major regulatory node in cilia and flagella. 2009, Pubmed
Heuser, The CSC connects three major axonemal complexes involved in dynein regulation. 2012, Pubmed
Heuser, Cryoelectron tomography reveals doublet-specific structures and unique interactions in the I1 dynein. 2012, Pubmed
Hirst, Ciliated air-liquid cultures as an aid to diagnostic testing of primary ciliary dyskinesia. 2010, Pubmed
Hirst, Culture of primary ciliary dyskinesia epithelial cells at air-liquid interface can alter ciliary phenotype but remains a robust and informative diagnostic aid. 2014, Pubmed
Hjeij, CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. 2014, Pubmed
Hjeij, ARMC4 mutations cause primary ciliary dyskinesia with randomization of left/right body asymmetry. 2013, Pubmed
Höben, Mutations in C11orf70 Cause Primary Ciliary Dyskinesia with Randomization of Left/Right Body Asymmetry Due to Defects of Outer and Inner Dynein Arms. 2018, Pubmed
Hockemeyer, Induced Pluripotent Stem Cells Meet Genome Editing. 2016, Pubmed
Höög, Cryo-electron tomography and 3-D analysis of the intact flagellum in Trypanosoma brucei. 2012, Pubmed
Hoque, CEP164 is essential for efferent duct multiciliogenesis and male fertility. 2021, Pubmed
Horani, Advances in the Genetics of Primary Ciliary Dyskinesia: Clinical Implications. 2018, Pubmed
Horani, Whole-exome capture and sequencing identifies HEATR2 mutation as a cause of primary ciliary dyskinesia. 2012, Pubmed
Horani, CCDC65 mutation causes primary ciliary dyskinesia with normal ultrastructure and hyperkinetic cilia. 2013, Pubmed
Horani, Primary ciliary dyskinesia and associated sensory ciliopathies. 2016, Pubmed
Hou, The N-terminus of IFT46 mediates intraflagellar transport of outer arm dynein and its cargo-adaptor ODA16. 2017, Pubmed
Hua, Noninvasive real-time measurement of nasal mucociliary clearance in mice by pinhole gamma scintigraphy. 2010, Pubmed
Huang, Paralyzed flagella mutants of Chlamydomonas reinhardtii. Defective for axonemal doublet microtubule arms. 1979, Pubmed
Hutchings, Trypanin is a cytoskeletal linker protein and is required for cell motility in African trypanosomes. 2002, Pubmed
Imhof, Cryo electron tomography with volta phase plate reveals novel structural foundations of the 96-nm axonemal repeat in the pathogen Trypanosoma brucei. 2019, Pubmed
Jafek, Ultrastructure of human nasal mucosa. 1983, Pubmed
Jaffe, c21orf59/kurly Controls Both Cilia Motility and Polarization. 2016, Pubmed , Xenbase
Jain, Sensory functions of motile cilia and implication for bronchiectasis. 2012, Pubmed
Jenkins, Olfactory cilia: linking sensory cilia function and human disease. 2009, Pubmed
Jiang, Total internal reflection fluorescence microscopy of intraflagellar transport in Tetrahymena thermophila. 2015, Pubmed
Jiao, Molecular genetics of infertility: loss-of-function mutations in humans and corresponding knockout/mutated mice. 2021, Pubmed
Jinkerson, Molecular techniques to interrogate and edit the Chlamydomonas nuclear genome. 2015, Pubmed
Joachimiak, Composition and function of the C1b/C1f region in the ciliary central apparatus. 2021, Pubmed
Kabututu, CMF70 is a subunit of the dynein regulatory complex. 2010, Pubmed
Kalueff, Zebrafish as an emerging model for studying complex brain disorders. 2014, Pubmed
Kamiya, Mutations at twelve independent loci result in absence of outer dynein arms in Chylamydomonas reinhardtii. 1988, Pubmed
Kang, Development of a pVEC peptide-based ribonucleoprotein (RNP) delivery system for genome editing using CRISPR/Cas9 in Chlamydomonas reinhardtii. 2020, Pubmed
Kempeneers, To beat, or not to beat, that is question! The spectrum of ciliopathies. 2018, Pubmed
Khan, Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families. 2021, Pubmed
Khan, Assembly, Functions and Evolution of Archaella, Flagella and Cilia. 2018, Pubmed
Kherraf, A Homozygous Ancestral SVA-Insertion-Mediated Deletion in WDR66 Induces Multiple Morphological Abnormalities of the Sperm Flagellum and Male Infertility. 2018, Pubmed
Kiesel, The molecular structure of mammalian primary cilia revealed by cryo-electron tomography. 2020, Pubmed
Kikuchi, Fine structure of guinea pig vestibular kinocilium. 1989, Pubmed
Kimmel, Stages of embryonic development of the zebrafish. 1995, Pubmed , Xenbase
Kindle, High-frequency nuclear transformation of Chlamydomonas reinhardtii. 1990, Pubmed
Kindle, Stable nuclear transformation of Chlamydomonas using the Chlamydomonas gene for nitrate reductase. 1989, Pubmed
King, The oligomeric outer dynein arm assembly factor CCDC103 is tightly integrated within the ciliary axoneme and exhibits periodic binding to microtubules. 2015, Pubmed
King, Planaria as a Model System for the Analysis of Ciliary Assembly and Motility. 2016, Pubmed
Kostiuk, Xenopus as a platform for discovery of genes relevant to human disease. 2021, Pubmed , Xenbase
Kott, Loss-of-function mutations in LRRC6, a gene essential for proper axonemal assembly of inner and outer dynein arms, cause primary ciliary dyskinesia. 2012, Pubmed
Kramer-Zucker, Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis. 2005, Pubmed
Krüger, Motility Analysis of Trypanosomatids. 2020, Pubmed
Kurkowiak, ZMYND10--Mutation Analysis in Slavic Patients with Primary Ciliary Dyskinesia. 2016, Pubmed
Kyuji, Cilia Loss and Dynein Assembly Defects in Planaria Lacking an Outer Dynein Arm-Docking Complex Subunit. 2020, Pubmed
Lander, State-of-the-art CRISPR/Cas9 Technology for Genome Editing in Trypanosomatids. 2019, Pubmed
Langousis, Motility and more: the flagellum of Trypanosoma brucei. 2014, Pubmed
Lechtreck, Chlamydomonas reinhardtii hydin is a central pair protein required for flagellar motility. 2007, Pubmed
Lee, Riding the wave of ependymal cilia: genetic susceptibility to hydrocephalus in primary ciliary dyskinesia. 2013, Pubmed
Lee, Motile cilia genetics and cell biology: big results from little mice. 2021, Pubmed
Legendre, Motile cilia and airway disease. 2021, Pubmed
Lehti, Cilia-related protein SPEF2 regulates osteoblast differentiation. 2018, Pubmed
Lehti, SPEF2 functions in microtubule-mediated transport in elongating spermatids to ensure proper male germ cell differentiation. 2017, Pubmed
Leigh, Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. 2009, Pubmed
Lesko, Dynein assembly factor with WD repeat domains 1 (DAW1) is required for the function of motile cilia in the planarian Schmidtea mediterranea. 2020, Pubmed
Leventea, Analysis of cilia structure and function in zebrafish. 2016, Pubmed
Lewis, Transcriptional regulation of multiciliated cell differentiation. 2021, Pubmed
Li, Characterisation of centriole biogenesis during multiciliation in planarians. 2020, Pubmed
Li, A genome-wide algal mutant library and functional screen identifies genes required for eukaryotic photosynthesis. 2019, Pubmed
Li, An Indexed, Mapped Mutant Library Enables Reverse Genetics Studies of Biological Processes in Chlamydomonas reinhardtii. 2016, Pubmed
Li, Biallelic mutations of CFAP251 cause sperm flagellar defects and human male infertility. 2019, Pubmed
Lin, FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia. 2019, Pubmed
Lin, Genetic and genomic approaches to identify genes involved in flagellar assembly in Chlamydomonas reinhardtii. 2015, Pubmed
Little, Right, left and cilia: How asymmetry is established. 2021, Pubmed
Liu, Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros. 2007, Pubmed
Liu, Loss-of-function mutations in SPEF2 cause multiple morphological abnormalities of the sperm flagella (MMAF). 2019, Pubmed
Liu, CFAP61 is required for sperm flagellum formation and male fertility in human and mouse. 2021, Pubmed
Liu, Three types of ependymal cells with intracellular calcium oscillation are characterized by distinct cilia beating properties. 2014, Pubmed
Liu, Homozygous mutations in SPEF2 induce multiple morphological abnormalities of the sperm flagella and male infertility. 2020, Pubmed
Lobo, Modeling planarian regeneration: a primer for reverse-engineering the worm. 2012, Pubmed
Loges, Recessive DNAH9 Loss-of-Function Mutations Cause Laterality Defects and Subtle Respiratory Ciliary-Beating Defects. 2018, Pubmed
Loges, DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer dynein arm. 2008, Pubmed
Lorencova, Ependymal cells surface of human third brain ventricle by scanning electron microscopy. 2020, Pubmed
Lorès, Mutations in TTC29, Encoding an Evolutionarily Conserved Axonemal Protein, Result in Asthenozoospermia and Male Infertility. 2019, Pubmed
Lu, Mcidas mutant mice reveal a two-step process for the specification and differentiation of multiciliated cells in mammals. 2019, Pubmed
Lyons, The reproductive significance of human Fallopian tube cilia. 2006, Pubmed
Ma, Bi-allelic mutations in MCIDAS and CCNO cause human infertility associated with abnormal gamete transport. 2021, Pubmed
MacGregor, Stable transformation of pleomorphic bloodstream form Trypanosoma brucei. 2013, Pubmed
MacRae, The fine structure of sensory receptor processes in the auricular epithelium of the planarian, Dugesia tigrina. 1967, Pubmed
Mali, ZMYND10 functions in a chaperone relay during axonemal dynein assembly. 2018, Pubmed
Malicki, Analysis of cilia structure and function in zebrafish. 2011, Pubmed
Marthin, Patient-specific three-dimensional explant spheroids derived from human nasal airway epithelium: a simple methodological approach for ex vivo studies of primary ciliary dyskinesia. 2017, Pubmed
Martinez, Biallelic variants in MAATS1 encoding CFAP91, a calmodulin-associated and spoke-associated complex protein, cause severe astheno-teratozoospermia and male infertility. 2020, Pubmed
Matsuo, The establishment of rotational polarity in the airway and ependymal cilia: analysis with a novel cilium motility mutant mouse. 2013, Pubmed
McKanna, Fine structure of the protonephridial system in Planaria. I. Flame cells. 1968, Pubmed
McKenzie, Strain-specific differences in brain gene expression in a hydrocephalic mouse model with motile cilia dysfunction. 2018, Pubmed
Merryman, Culturing Planarians in the Laboratory. 2018, Pubmed
Mirzadeh, Bi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories. 2017, Pubmed
Mitchell, Evolution of Cilia. 2017, Pubmed
Mitchell, Reversion analysis of dynein intermediate chain function. 1993, Pubmed
Mitchison, Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia. 2012, Pubmed
Mitchison, Motile and non-motile cilia in human pathology: from function to phenotypes. 2017, Pubmed
Moore, Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia. 2013, Pubmed
Morgan, An evolutionarily conserved coiled-coil protein implicated in polycystic kidney disease is involved in basal body duplication and flagellar biogenesis in Trypanosoma brucei. 2005, Pubmed
Motta, Electron Microscopy Techniques Applied to Symbiont-Harboring Trypanosomatids: The Association of the Bacterium with Host Organelles. 2020, Pubmed
Munye, BMI-1 extends proliferative potential of human bronchial epithelial cells while retaining their mucociliary differentiation capacity. 2017, Pubmed
Muthusamy, A knock-in Foxj1(CreERT2::GFP) mouse for recombination in epithelial cells with motile cilia. 2014, Pubmed
Neugebauer, Ciliogenesis in submersion and suspension cultures of human nasal epithelial cells. 2003, Pubmed
Nonaka, Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. 1998, Pubmed
Oberholzer, Approaches for functional analysis of flagellar proteins in African trypanosomes. 2009, Pubmed
Oda, A molecular ruler determines the repeat length in eukaryotic cilia and flagella. 2014, Pubmed
Oji, CRISPR/Cas9 mediated genome editing in ES cells and its application for chimeric analysis in mice. 2016, Pubmed
Olbrich, Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. 2002, Pubmed
Olmstead, Reproductive maturation of the tropical clawed frog: Xenopus tropicalis. 2009, Pubmed , Xenbase
Olstad, Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development. 2019, Pubmed
Omran, Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins. 2008, Pubmed
Osinka, Ciliary Proteins: Filling the Gaps. Recent Advances in Deciphering the Protein Composition of Motile Ciliary Complexes. 2019, Pubmed
Owa, Inner lumen proteins stabilize doublet microtubules in cilia and flagella. 2019, Pubmed
Panizzi, CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. 2012, Pubmed
Park, Modification of a Chlamydomonas reinhardtii CRISPR/Cas9 transformation protocol for use with widely available electroporation equipment. 2020, Pubmed
Pazour, Proteomic analysis of a eukaryotic cilium. 2005, Pubmed
Pazour, The vertebrate primary cilium is a sensory organelle. 2003, Pubmed
Pennarun, Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. 1999, Pubmed
Peters, The mouse as a model for human biology: a resource guide for complex trait analysis. 2007, Pubmed
Picariello, TIM, a targeted insertional mutagenesis method utilizing CRISPR/Cas9 in Chlamydomonas reinhardtii. 2020, Pubmed
Pifferi, Simplified cell culture method for the diagnosis of atypical primary ciliary dyskinesia. 2009, Pubmed
Pigino, Cryoelectron tomography of radial spokes in cilia and flagella. 2011, Pubmed
Pinto, Zebrafish Motile Cilia as a Model for Primary Ciliary Dyskinesia. 2021, Pubmed
Poprzeczko, Rare Human Diseases: Model Organisms in Deciphering the Molecular Basis of Primary Ciliary Dyskinesia. 2019, Pubmed , Xenbase
Rachev, CFAP43 modulates ciliary beating in mouse and Xenopus. 2020, Pubmed , Xenbase
Rajagopalan, Analysis of properties of cilia using Tetrahymena thermophila. 2009, Pubmed
Ralston, Flagellar motility contributes to cytokinesis in Trypanosoma brucei and is modulated by an evolutionarily conserved dynein regulatory system. 2006, Pubmed
Rao, Xenopus to the rescue: A model to validate and characterize candidate ciliopathy genes. 2021, Pubmed , Xenbase
Reiter, Genes and molecular pathways underpinning ciliopathies. 2017, Pubmed
Ringers, The role of motile cilia in the development and physiology of the nervous system. 2020, Pubmed
Rink, The maintenance and regeneration of the planarian excretory system are regulated by EGFR signaling. 2011, Pubmed
Rodriguez, Lessons From Unilateral Loss of Cilia: Early Nasal Nitric Oxide Gas Mixing and the Role of Sinus Patency in Determining Nasal Nitric Oxide. 2017, Pubmed
Rompolas, Analysis of ciliary assembly and function in planaria. 2013, Pubmed
Rosenthal, The mouse ascending: perspectives for human-disease models. 2007, Pubmed
Rotureau, Molecular bases of cytoskeleton plasticity during the Trypanosoma brucei parasite cycle. 2011, Pubmed
Rupp, The sup-pf-2 mutations of Chlamydomonas alter the activity of the outer dynein arms by modification of the gamma-dynein heavy chain. 1996, Pubmed
Ruzicka, The Zebrafish Information Network: new support for non-coding genes, richer Gene Ontology annotations and the Alliance of Genome Resources. 2019, Pubmed
Sahabian, Generation of two hiPSC clones (MHHi019-A, MHHi019-B) from a primary ciliary dyskinesia patient carrying a homozygous deletion in the NME5 gene (c.415delA (p.Ile139Tyrfs*8)). 2020, Pubmed
Salanga, Genotype to Phenotype: CRISPR Gene Editing Reveals Genetic Compensation as a Mechanism for Phenotypic Disjunction of Morphants and Mutants. 2021, Pubmed
Salomé, A Series of Fortunate Events: Introducing Chlamydomonas as a Reference Organism. 2019, Pubmed
Samsel, Central Apparatus, the Molecular Kickstarter of Ciliary and Flagellar Nanomachines. 2021, Pubmed
Santi-Rocca, Imaging intraflagellar transport in trypanosomes. 2015, Pubmed
Schamberger, Cigarette smoke alters primary human bronchial epithelial cell differentiation at the air-liquid interface. 2015, Pubmed
Schmitz, A novel Cre-inducible knock-in ARL13B-tRFP fusion cilium reporter. 2017, Pubmed
Schweickert, Cilia-driven leftward flow determines laterality in Xenopus. 2007, Pubmed , Xenbase
Sedykh, Novel roles for the radial spoke head protein 9 in neural and neurosensory cilia. 2016, Pubmed
Serres, Ultrastructural morphometry of the human sperm flagellum with a stereological analysis of the lengths of the dense fibres. 1983, Pubmed
Session, Genome evolution in the allotetraploid frog Xenopus laevis. 2016, Pubmed , Xenbase
Sha, Biallelic mutations in Sperm flagellum 2 cause human multiple morphological abnormalities of the sperm flagella (MMAF) phenotype. 2019, Pubmed
Sha, Novel Mutations in CFAP44 and CFAP43 Cause Multiple Morphological Abnormalities of the Sperm Flagella (MMAF). 2019, Pubmed
Shah, Motile cilia of human airway epithelia are chemosensory. 2009, Pubmed
Shang, A robust inducible-repressible promoter greatly facilitates gene knockouts, conditional expression, and overexpression of homologous and heterologous genes in Tetrahymena thermophila. 2002, Pubmed
Shen, Bi-allelic truncating variants in CFAP206 cause male infertility in human and mouse. 2021, Pubmed
Shi, Primary ciliary dyskinesia relative protein ZMYND10 is involved in regulating ciliary function and intraflagellar transport in Paramecium tetraurelia. 2021, Pubmed
Shimogawara, High-efficiency transformation of Chlamydomonas reinhardtii by electroporation. 1998, Pubmed
Shin, CRISPR/Cas9-induced knockout and knock-in mutations in Chlamydomonas reinhardtii. 2016, Pubmed
Shinohara, Cilia in Left-Right Symmetry Breaking. 2017, Pubmed
Sironen, Loss of SPEF2 function in mice results in spermatogenesis defects and primary ciliary dyskinesia. 2011, Pubmed
Smith, Robust method for proteome analysis by MS/MS using an entire translated genome: demonstration on the ciliome of Tetrahymena thermophila. 2005, Pubmed
Smith, PF16 encodes a protein with armadillo repeats and localizes to a single microtubule of the central apparatus in Chlamydomonas flagella. 1996, Pubmed
Soares Medeiros, Rapid, Selection-Free, High-Efficiency Genome Editing in Protozoan Parasites Using CRISPR-Cas9 Ribonucleoproteins. 2017, Pubmed
Sobkowicz, The kinocilium of auditory hair cells and evidence for its morphogenetic role during the regeneration of stereocilia and cuticular plates. 1995, Pubmed
Solomon, Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography. 2017, Pubmed
Song, Zebrafish as a Model for Human Ciliopathies. 2016, Pubmed
Stubbs, The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos. 2008, Pubmed , Xenbase
Stubbs, Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation. 2012, Pubmed , Xenbase
Subota, Proteomic analysis of intact flagella of procyclic Trypanosoma brucei cells identifies novel flagellar proteins with unique sub-localization and dynamics. 2014, Pubmed
Sun, Three-dimensional architecture of epithelial primary cilia. 2019, Pubmed
Suzuki, Differentiation of human pluripotent stem cells into functional airway basal stem cells. 2021, Pubmed
Tan, Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia. 2007, Pubmed
Tandon, Expanding the genetic toolkit in Xenopus: Approaches and opportunities for human disease modeling. 2017, Pubmed , Xenbase
Tang, Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella. 2017, Pubmed
Tarkar, DYX1C1 is required for axonemal dynein assembly and ciliary motility. 2013, Pubmed
Taschner, Structural basis of outer dynein arm intraflagellar transport by the transport adaptor protein ODA16 and the intraflagellar transport protein IFT46. 2017, Pubmed
Tassin, Paramecium tetraurelia basal body structure. 2015, Pubmed
Tavares, Notch/Her12 signalling modulates, motile/immotile cilia ratio downstream of Foxj1a in zebrafish left-right organizer. 2017, Pubmed
Terré, Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice. 2019, Pubmed
Thomas, TTC12 Loss-of-Function Mutations Cause Primary Ciliary Dyskinesia and Unveil Distinct Dynein Assembly Mechanisms in Motile Cilia Versus Flagella. 2020, Pubmed
Tobin, The nonmotile ciliopathies. 2009, Pubmed
Touré, The genetic architecture of morphological abnormalities of the sperm tail. 2021, Pubmed
Tu, Novel mutations in SPEF2 causing different defects between flagella and cilia bridge: the phenotypic link between MMAF and PCD. 2020, Pubmed
Tuxhorn, Regulation of flagellar length in Chlamydomonas. 1998, Pubmed
Urbanska, Ciliary proteins Fap43 and Fap44 interact with each other and are essential for proper cilia and flagella beating. 2018, Pubmed
Urbanska, The CSC proteins FAP61 and FAP251 build the basal substructures of radial spoke 3 in cilia. 2015, Pubmed
Valentine, Using Paramecium as a Model for Ciliopathies. 2021, Pubmed
Vasudevan, FAP206 is a microtubule-docking adapter for ciliary radial spoke 2 and dynein c. 2015, Pubmed
Veres, Intubation-free in vivo imaging of the tracheal mucosa using two-photon microscopy. 2017, Pubmed
Vertii, New frontiers: discovering cilia-independent functions of cilia proteins. 2015, Pubmed
Vij, Evolutionarily ancient association of the FoxJ1 transcription factor with the motile ciliogenic program. 2012, Pubmed
Vincensini, 1001 model organisms to study cilia and flagella. 2011, Pubmed , Xenbase
Vladar, Analysis of ciliogenesis in primary culture mouse tracheal epithelial cells. 2013, Pubmed
Wakabayashi, Axonemal motility in Chlamydomonas. 2015, Pubmed
Walentek, What we can learn from a tadpole about ciliopathies and airway diseases: Using systems biology in Xenopus to study cilia and mucociliary epithelia. 2017, Pubmed , Xenbase
Wallmeier, Motile ciliopathies. 2020, Pubmed
Wallmeier, De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left/Right Body Asymmetry. 2019, Pubmed
Wallmeier, Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia. 2014, Pubmed , Xenbase
Wallmeier, TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization. 2016, Pubmed , Xenbase
Wang, The Kinocilia of Cochlear Hair Cells: Structures, Functions, and Diseases. 2021, Pubmed
Wang, In vivo micro-scale tomography of ciliary behavior in the mammalian oviduct. 2015, Pubmed
Wensel, Structural and molecular bases of rod photoreceptor morphogenesis and disease. 2016, Pubmed
Wensel, Structure and dynamics of photoreceptor sensory cilia. 2021, Pubmed
Werner, Understanding ciliated epithelia: the power of Xenopus. 2012, Pubmed , Xenbase
Werner, Using Xenopus skin to study cilia development and function. 2013, Pubmed , Xenbase
Wilkerson, The 78,000 M(r) intermediate chain of Chlamydomonas outer arm dynein isa WD-repeat protein required for arm assembly. 1995, Pubmed
Williams, Molecular cloning and sequence analysis of the Chlamydomonas gene coding for radial spoke protein 3: flagellar mutation pf-14 is an ochre allele. 1989, Pubmed
Wilson, Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis. 2009, Pubmed
Winey, Cytological analysis of Tetrahymena thermophila. 2012, Pubmed
Wirtz, A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei. 1999, Pubmed
Wlizla, Generation and Care of Xenopus laevis and Xenopus tropicalis Embryos. 2018, Pubmed , Xenbase
Wloga, From molecules to morphology: cellular organization of Tetrahymena thermophila. 2012, Pubmed
Wloga, Members of the NIMA-related kinase family promote disassembly of cilia by multiple mechanisms. 2006, Pubmed
WORTHINGTON, Ependymal cilia: distribution and activity in the adult human brain. 1963, Pubmed
Wu, Patients with severe asthenoteratospermia carrying SPAG6 or RSPH3 mutations have a positive pregnancy outcome following intracytoplasmic sperm injection. 2020, Pubmed
Wu, NovelCFAP43 andCFAP44 mutations cause male infertility with multiple morphological abnormalities of the sperm flagella (MMAF). 2019, Pubmed
Xu, Establishment of an induced pluripotent stem cell line from a patient with primary ciliary dyskinesia carrying biallelic mutations in CCNO. 2021, Pubmed
Xu, Characterization of tetratricopeptide repeat-containing proteins critical for cilia formation and function. 2015, Pubmed
Yagoubat, Gene Editing in Trypanosomatids: Tips and Tricks in the CRISPR-Cas9 Era. 2020, Pubmed
Yamamoto, The MIA complex is a conserved and novel dynein regulator essential for normal ciliary motility. 2013, Pubmed
Yamamoto, Chlamydomonas DYX1C1/PF23 is essential for axonemal assembly and proper morphology of inner dynein arms. 2017, Pubmed
Yamamoto, Discrete PIH proteins function in the cytoplasmic preassembly of different subsets of axonemal dyneins. 2010, Pubmed
Yamamoto, Mutations in PIH proteins MOT48, TWI1 and PF13 define common and unique steps for preassembly of each, different ciliary dynein. 2020, Pubmed
Yang, Radial spoke proteins of Chlamydomonas flagella. 2006, Pubmed
Yin, Mice with a Deletion of Rsph1 Exhibit a Low Level of Mucociliary Clearance and Develop a Primary Ciliary Dyskinesia Phenotype. 2019, Pubmed
Yu, Foxj1 transcription factors are master regulators of the motile ciliogenic program. 2008, Pubmed
Yuan, Motile cilia of the male reproductive system require miR-34/miR-449 for development and function to generate luminal turbulence. 2019, Pubmed
Zariwala, ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6. 2013, Pubmed , Xenbase
Zhang, Cpc1, a Chlamydomonas central pair protein with an adenylate kinase domain. 2004, Pubmed
Zhang, Basal bodies in Xenopus. 2015, Pubmed , Xenbase
Zhou, Conservation as well as divergence in Mcidas function underlies the differentiation of multiciliated cells in vertebrates. 2020, Pubmed
Zietkiewicz, CFAP300: Mutations in Slavic Patients with Primary Ciliary Dyskinesia and a Role in Ciliary Dynein Arms Trafficking. 2019, Pubmed