XB-ART-53024
Genesis
2017 Jan 01;551-2:. doi: 10.1002/dvg.23001.
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What we can learn from a tadpole about ciliopathies and airway diseases: Using systems biology in Xenopus to study cilia and mucociliary epithelia.
Walentek P
,
Quigley IK
.
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Over the past years, the Xenopus embryo has emerged as an incredibly useful model organism for studying the formation and function of cilia and ciliated epithelia in vivo. This has led to a variety of findings elucidating the molecular mechanisms of ciliated cell specification, basal body biogenesis, cilia assembly, and ciliary motility. These findings also revealed the deep functional conservation of signaling, transcriptional, post-transcriptional, and protein networks employed in the formation and function of vertebrate ciliated cells. Therefore, Xenopus research can contribute crucial insights not only into developmental and cell biology, but also into the molecular mechanisms underlying cilia related diseases (ciliopathies) as well as diseases affecting the ciliated epithelium of the respiratory tract in humans (e.g., chronic lung diseases). Additionally, systems biology approaches including transcriptomics, genomics, and proteomics have been rapidly adapted for use in Xenopus, and broaden the applications for current and future translational biomedical research. This review aims to present the advantages of using Xenopus for cilia research, highlight some of the evolutionarily conserved key concepts and mechanisms of ciliated cell biology that were elucidated using the Xenopus model, and describe the potential for Xenopus research to address unresolved questions regarding the molecular mechanisms of ciliopathies and airway diseases.
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K99 HL127275 NHLBI NIH HHS
Species referenced: Xenopus laevis
Genes referenced: bmp4 ccp110 cetn4 e2f4 e2f5 foxa1 foxj1 foxj1.2 foxn4 gmnc mab21l1 mcc mcidas myb nkx2-2 notch1 pax6 pitx2 rfx2 rfx3 tfdp1 tp73 tuba4b wnt1
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Figure 1. Ciliated tissues in Xenopus laevis embryos and tadpoles. Immunofluorescent staining of Xenopus laevis embryos with anti-acetylated-α-tubulin antibody to reveal cilia (green) of (A) the gastrocoel roof plate (GRP) at stage 17, (B) the neural tube at stage 26, and (C) the embryonic mucociliary epidermis at stage 32. The different types of ciliated cells are shown in magnified views. Co-staining: Phalloidin for F-actin (red), anti-serotonin for small secretory cells (5HT; blue). Basal bodies were visualized by expression of centrin4-rfp (red) and gfp-cp110 (blue). Digitized images and developmental data from Nieuwkoop and Faber (1994) Normal Table of Xenopus laevis (Daudin) were obtained from Xenbase.org |
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Figure 2. Transcriptional and post-transcriptional regulation of multi-ciliated cells. (A) Transcriptional control of core MCC gene expression in multi-ciliated cells. Arrows = activation, T = inhibition, solid line = major contribution, dotted line = supporting contribution. (B) A transcriptional/post-transcriptional regulatory module titrates levels of Cp110 to allow for ciliogenesis in MCCs. Left panel: cp110, miR-34b/c, and miR-449a-c are directly regulated by ciliary transcription factors (color code is the same as in A). Right panel: optimal (intermediate) Cp110 levels are required for ciliogenesis. Summary of effects of too much or too little Cp110 on MCC cilia formation |
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Figure 3. Signaling regulation in the Xenopus mucociliary epidermis. Overview of signaling regulation and development of the mucociliary epidermis. (A) Developmental processes over the time-course of mucociliary epithelium formation. Corresponding stages of Xenopus development are depicted on the left. Digitized images and developmental data from Nieuwkoop and Faber (1994) Normal Table of Xenopus laevis (Daudin) were obtained from Xenbase.org. (B) Schematic summary of signaling events and key transcription factors regulating mucociliary cell fate specification. Binary decisions based on high versus low level input from signaling events are shown as triangle representing two sides of a signaling gradient (for BMP, Wnt and Notch). Additional contributions from signaling pathways are depicted as, for example, “+Wnt.†In later stages, BMP signaling (yellow) is also required for intercalation of all cell types derived from subepithelial progenitors |
References [+] :
Afzelius,
A human syndrome caused by immotile cilia.
1976, Pubmed
Afzelius, A human syndrome caused by immotile cilia. 1976, Pubmed
Asashima, In vitro organogenesis from undifferentiated cells in Xenopus. 2009, Pubmed , Xenbase
Avasthi, Stages of ciliogenesis and regulation of ciliary length. 2012, Pubmed
Barker, Bioinformatic analysis of ciliary transition zone proteins reveals insights into the evolution of ciliopathy networks. 2014, Pubmed
Beers, The three R's of lung health and disease: repair, remodeling, and regeneration. 2011, Pubmed
Berbari, The primary cilium as a complex signaling center. 2009, Pubmed
Bhattacharya, CRISPR/Cas9: An inexpensive, efficient loss of function tool to screen human disease genes in Xenopus. 2015, Pubmed , Xenbase
Blitz, Biallelic genome modification in F(0) Xenopus tropicalis embryos using the CRISPR/Cas system. 2013, Pubmed , Xenbase
Blum, The evolution and conservation of left-right patterning mechanisms. 2014, Pubmed , Xenbase
Blum, Morpholinos: Antisense and Sensibility. 2015, Pubmed , Xenbase
Blum, Xenopus, an ideal model system to study vertebrate left-right asymmetry. 2009, Pubmed , Xenbase
Blum, Ciliation and gene expression distinguish between node and posterior notochord in the mammalian embryo. 2007, Pubmed , Xenbase
Bogdanović, Active DNA demethylation at enhancers during the vertebrate phylotypic period. 2016, Pubmed , Xenbase
Boskovski, The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. 2013, Pubmed , Xenbase
Brechbuhl, β-catenin dosage is a critical determinant of tracheal basal cell fate determination. 2011, Pubmed
Brooks, Multiciliated cells. 2014, Pubmed
Brooks, In vivo investigation of cilia structure and function using Xenopus. 2015, Pubmed , Xenbase
Butler, Control of vertebrate core planar cell polarity protein localization and dynamics by Prickle 2. 2015, Pubmed , Xenbase
Campbell, Foxn4 promotes gene expression required for the formation of multiple motile cilia. 2016, Pubmed , Xenbase
Caron, Wnt/β-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer's vesicle. 2012, Pubmed
Chalmers, Development of the gut in Xenopus laevis. 1998, Pubmed , Xenbase
Choksi, Switching on cilia: transcriptional networks regulating ciliogenesis. 2014, Pubmed
Chung, RFX2 is broadly required for ciliogenesis during vertebrate development. 2012, Pubmed , Xenbase
Chung, Sp8 regulates inner ear development. 2014, Pubmed , Xenbase
Chung, Coordinated genomic control of ciliogenesis and cell movement by RFX2. 2014, Pubmed , Xenbase
Cibois, BMP signalling controls the construction of vertebrate mucociliary epithelia. 2015, Pubmed , Xenbase
Crystal, Airway epithelial cells: current concepts and challenges. 2008, Pubmed
Davenport, An incredible decade for the primary cilium: a look at a once-forgotten organelle. 2005, Pubmed
Deblandre, A two-step mechanism generates the spacing pattern of the ciliated cells in the skin of Xenopus embryos. 1999, Pubmed , Xenbase
De Langhe, Wnt signaling in lung organogenesis. 2008, Pubmed
Dessaud, Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network. 2008, Pubmed
Dubaissi, A secretory cell type develops alongside multiciliated cells, ionocytes and goblet cells, and provides a protective, anti-infective function in the frog embryonic mucociliary epidermis. 2014, Pubmed , Xenbase
Eisen, Controlling morpholino experiments: don't stop making antisense. 2008, Pubmed , Xenbase
ELKAN, New lateral line sensory organs in Xenopus laevis Daudin. 1951, Pubmed , Xenbase
Falk, Specialized Cilia in Mammalian Sensory Systems. 2015, Pubmed
Freund, Fluid flows and forces in development: functions, features and biophysical principles. 2012, Pubmed
Fulcher, Well-differentiated human airway epithelial cell cultures. 2005, Pubmed
Ganesan, Barrier function of airway tract epithelium. 2013, Pubmed
Ganesan, Repair and Remodeling of airway epithelium after injury in Chronic Obstructive Pulmonary Disease. 2013, Pubmed
Gentzel, Distinct functionality of dishevelled isoforms on Ca2+/calmodulin-dependent protein kinase 2 (CamKII) in Xenopus gastrulation. 2015, Pubmed , Xenbase
Ghosh, Regulation of trachebronchial tissue-specific stem cell pool size. 2013, Pubmed
Gomi, Activation of NOTCH1 or NOTCH3 signaling skews human airway basal cell differentiation toward a secretory pathway. 2015, Pubmed
Graff, Cigarette smoking decreases global microRNA expression in human alveolar macrophages. 2012, Pubmed
Grant, The Xenopus ORFeome: A resource that enables functional genomics. 2015, Pubmed , Xenbase
Gurdon, The introduction of Xenopus laevis into developmental biology: of empire, pregnancy testing and ribosomal genes. 2000, Pubmed , Xenbase
Hagenlocher, Ciliogenesis and cerebrospinal fluid flow in the developing Xenopus brain are regulated by foxj1. 2013, Pubmed , Xenbase
Harland, Xenopus research: metamorphosed by genetics and genomics. 2011, Pubmed , Xenbase
Hayes, Identification of novel ciliogenesis factors using a new in vivo model for mucociliary epithelial development. 2007, Pubmed , Xenbase
Heasman, Patterning the Xenopus blastula. 1997, Pubmed , Xenbase
Hellsten, The genome of the Western clawed frog Xenopus tropicalis. 2010, Pubmed , Xenbase
Herriges, Lung development: orchestrating the generation and regeneration of a complex organ. 2014, Pubmed
Hruscha, Efficient CRISPR/Cas9 genome editing with low off-target effects in zebrafish. 2013, Pubmed
Hsu, Repair of naphthalene-induced acute tracheal injury by basal cells depends on β-catenin. 2014, Pubmed
Ibañez-Tallon, To beat or not to beat: roles of cilia in development and disease. 2003, Pubmed
Karpinka, Xenbase, the Xenopus model organism database; new virtualized system, data types and genomes. 2015, Pubmed , Xenbase
Kemp, Role of epidermal cilia in development of the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi). 1996, Pubmed
Kjolby, Genome-wide identification of Wnt/β-catenin transcriptional targets during Xenopus gastrulation. 2017, Pubmed , Xenbase
König, Planar polarity in the ciliated epidermis of Xenopus embryos. 1993, Pubmed , Xenbase
Lamouille, Molecular mechanisms of epithelial-mesenchymal transition. 2014, Pubmed
Lienkamp, Inversin relays Frizzled-8 signals to promote proximal pronephros development. 2010, Pubmed , Xenbase
Lizé, MicroRNA-449a levels increase by several orders of magnitude during mucociliary differentiation of airway epithelia. 2010, Pubmed
Ma, Multicilin drives centriole biogenesis via E2f proteins. 2014, Pubmed , Xenbase
Marcet, Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway. 2011, Pubmed , Xenbase
Marshall, Cilia orientation and the fluid mechanics of development. 2008, Pubmed
Marshall, p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network. 2016, Pubmed
Mitchell, A positive feedback mechanism governs the polarity and motion of motile cilia. 2007, Pubmed , Xenbase
Moreno-Mateos, CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. 2015, Pubmed , Xenbase
Morimoto, Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells. 2012, Pubmed
Mucenski, Beta-catenin regulates differentiation of respiratory epithelial cells in vivo. 2005, Pubmed
Nakayama, Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus tropicalis. 2013, Pubmed , Xenbase
Nemajerova, TAp73 is a central transcriptional regulator of airway multiciliogenesis. 2016, Pubmed
Okubo, Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm. 2004, Pubmed
Ossipova, PAR1 specifies ciliated cells in vertebrate ectoderm downstream of aPKC. 2007, Pubmed , Xenbase
Pain, Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype. 2014, Pubmed
Pan, Myb permits multilineage airway epithelial cell differentiation. 2014, Pubmed
Peshkin, On the Relationship of Protein and mRNA Dynamics in Vertebrate Embryonic Development. 2015, Pubmed , Xenbase
Pongracz, Wnt signalling in lung development and diseases. 2006, Pubmed
Quigley, Rfx2 Stabilizes Foxj1 Binding at Chromatin Loops to Enable Multiciliated Cell Gene Expression. 2017, Pubmed , Xenbase
Quigley, Specification of ion transport cells in the Xenopus larval skin. 2011, Pubmed , Xenbase
Rock, Notch-dependent differentiation of adult airway basal stem cells. 2011, Pubmed
Rock, Basal cells as stem cells of the mouse trachea and human airway epithelium. 2009, Pubmed
Rock, Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. 2010, Pubmed
Ruptier, TP63 P2 promoter functional analysis identifies β-catenin as a key regulator of ΔNp63 expression. 2011, Pubmed
Satir, Overview of structure and function of mammalian cilia. 2007, Pubmed
Sattar, The ciliopathies in neuronal development: a clinical approach to investigation of Joubert syndrome and Joubert syndrome-related disorders. 2011, Pubmed
Schweickert, The nodal inhibitor Coco is a critical target of leftward flow in Xenopus. 2010, Pubmed , Xenbase
Schweickert, Cilia-driven leftward flow determines laterality in Xenopus. 2007, Pubmed , Xenbase
Schweickert, Linking early determinants and cilia-driven leftward flow in left-right axis specification of Xenopus laevis: a theoretical approach. 2012, Pubmed , Xenbase
Session, Genome evolution in the allotetraploid frog Xenopus laevis. 2016, Pubmed , Xenbase
Shah, Motile cilia of human airway epithelia are chemosensory. 2009, Pubmed
Song, miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110. 2014, Pubmed , Xenbase
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
Takahashi, mab21-l3 regulates cell fate specification of multiciliate cells and ionocytes. 2015, Pubmed , Xenbase
Tan, Myb promotes centriole amplification and later steps of the multiciliogenesis program. 2013, Pubmed , Xenbase
Tilley, Cilia dysfunction in lung disease. 2015, Pubmed
Tobin, Bardet-Biedl syndrome: beyond the cilium. 2007, Pubmed
Toriyama, The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery. 2016, Pubmed , Xenbase
Toriyama, Corrigendum: The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery. 2016, Pubmed
Treutlein, Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. 2014, Pubmed
Tsao, Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. 2009, Pubmed
Veleri, Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis. 2014, Pubmed
Verdugo, Introduction: mucociliary function in mammalian epithelia. 1982, Pubmed
Vick, Flow on the right side of the gastrocoel roof plate is dispensable for symmetry breakage in the frog Xenopus laevis. 2009, Pubmed , Xenbase
Walentek, ATP4a is required for development and function of the Xenopus mucociliary epidermis - a potential model to study proton pump inhibitor-associated pneumonia. 2015, Pubmed , Xenbase
Walentek, Ciliary transcription factors in cancer--how understanding ciliogenesis can promote the detection and prognosis of cancer types. 2016, Pubmed
Walentek, ATP4 and ciliation in the neuroectoderm and endoderm of Xenopus embryos and tadpoles. 2015, Pubmed , Xenbase
Walentek, Ciliary transcription factors and miRNAs precisely regulate Cp110 levels required for ciliary adhesions and ciliogenesis. 2016, Pubmed , Xenbase
Walentek, microRNAs and cilia. An ancient connection. 2014, Pubmed , Xenbase
Walentek, ATP4a is required for Wnt-dependent Foxj1 expression and leftward flow in Xenopus left-right development. 2012, Pubmed , Xenbase
Walentek, A novel serotonin-secreting cell type regulates ciliary motility in the mucociliary epidermis of Xenopus tadpoles. 2014, Pubmed , Xenbase
Wallingford, Planar cell polarity signaling, cilia and polarized ciliary beating. 2010, Pubmed
Wang, A systematic approach identifies FOXA1 as a key factor in the loss of epithelial traits during the epithelial-to-mesenchymal transition in lung cancer. 2013, Pubmed
Wang, miR-34b regulates multiciliogenesis during organ formation in zebrafish. 2013, Pubmed
Waters, Ciliopathies: an expanding disease spectrum. 2011, Pubmed
Werner, Understanding ciliated epithelia: the power of Xenopus. 2012, Pubmed , Xenbase
Werner, Actin and microtubules drive differential aspects of planar cell polarity in multiciliated cells. 2011, Pubmed , Xenbase
Werner, Using Xenopus skin to study cilia development and function. 2013, Pubmed , Xenbase
Wessely, Xenopus pronephros development--past, present, and future. 2011, Pubmed , Xenbase
Wong, The primary cilium at the crossroads of mammalian hedgehog signaling. 2008, Pubmed
Wühr, Deep proteomics of the Xenopus laevis egg using an mRNA-derived reference database. 2014, Pubmed , Xenbase
Zariwala, The emerging genetics of primary ciliary dyskinesia. 2011, Pubmed
Zhang, Centriole biogenesis and function in multiciliated cells. 2015, Pubmed , Xenbase
Zhang, Basal bodies in Xenopus. 2015, Pubmed , Xenbase
Zhou, Gmnc Is a Master Regulator of the Multiciliated Cell Differentiation Program. 2015, Pubmed , Xenbase
Zhou, Proximo-distal specialization of epithelial transport processes within the Xenopus pronephric kidney tubules. 2004, Pubmed , Xenbase
Zhou, Particle streak velocimetry-optical coherence tomography: a novel method for multidimensional imaging of microscale fluid flows. 2016, Pubmed , Xenbase
ZUCKERMAN, Kartagener's triad; review of the literature and report of a case. 1951, Pubmed