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  1. Article ; Online: Signaling Control of Mucociliary Epithelia: Stem Cells, Cell Fates, and the Plasticity of Cell Identity in Development and Disease.

    Walentek, Peter

    Cells, tissues, organs

    2021  Volume 211, Issue 6, Page(s) 736–753

    Abstract: Mucociliary epithelia are composed of multiciliated, secretory, and stem cells and line various organs in vertebrates such as the respiratory tract. By means of mucociliary clearance, those epithelia provide a first line of defense against inhaled ... ...

    Abstract Mucociliary epithelia are composed of multiciliated, secretory, and stem cells and line various organs in vertebrates such as the respiratory tract. By means of mucociliary clearance, those epithelia provide a first line of defense against inhaled particles and pathogens. Mucociliary clearance relies on the correct composition of cell types, that is, the proper balance of ciliated and secretory cells. A failure to generate and to maintain correct cell type composition and function results in impaired clearance and high risk to infections, such as in congenital diseases (e.g., ciliopathies) as well as in acquired diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). While it remains incompletely resolved how precisely cell types are specified and maintained in development and disease, many studies have revealed important mechanisms regarding the signaling control in mucociliary cell types in various species. Those studies not only provided insights into the signaling contribution to organ development and regeneration but also highlighted the remarkable plasticity of cell identity encountered in mucociliary maintenance, including frequent trans-differentiation events during homeostasis and specifically in disease. This review will summarize major findings and provide perspectives regarding the future of mucociliary research and the treatment of chronic airway diseases associated with tissue remodeling.
    MeSH term(s) Animals ; Epithelium/metabolism ; Signal Transduction ; Cell Differentiation ; Mucociliary Clearance/physiology ; Stem Cells ; Cilia/metabolism
    Language English
    Publishing date 2021-04-26
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1468141-9
    ISSN 1422-6421 ; 1422-6405
    ISSN (online) 1422-6421
    ISSN 1422-6405
    DOI 10.1159/000514579
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Xenopus epidermal and endodermal epithelia as models for mucociliary epithelial evolution, disease, and metaplasia.

    Walentek, Peter

    Genesis (New York, N.Y. : 2000)

    2021  Volume 59, Issue 1-2, Page(s) e23406

    Abstract: The Xenopus embryonic epidermis is a powerful model to study mucociliary biology, development, and disease. Particularly, the Xenopus system is being used to elucidate signaling pathways, transcription factor functions, and morphogenetic mechanisms ... ...

    Abstract The Xenopus embryonic epidermis is a powerful model to study mucociliary biology, development, and disease. Particularly, the Xenopus system is being used to elucidate signaling pathways, transcription factor functions, and morphogenetic mechanisms regulating cell fate specification, differentiation and cell function. Thereby, Xenopus research has provided significant insights into potential underlying molecular mechanisms for ciliopathies and chronic airway diseases. Recent studies have also established the embryonic epidermis as a model for mucociliary epithelial remodeling, multiciliated cell trans-differentiation, cilia loss, and mucus secretion. Additionally, the tadpole foregut epithelium is lined by a mucociliary epithelium, which shows remarkable features resembling mammalian airway epithelia, including its endodermal origin and a variable cell type composition along the proximal-distal axis. This review aims to summarize the advantages of the Xenopus epidermis for mucociliary epithelial biology and disease modeling. Furthermore, the potential of the foregut epithelium as novel mucociliary model system is being highlighted. Additional perspectives are presented on how to expand the range of diseases that can be modeled in the frog system, including proton pump inhibitor-associated pneumonia as well as metaplasia in epithelial cells of the airway and the gastroesophageal region.
    MeSH term(s) Animals ; Ciliopathies/metabolism ; Ciliopathies/pathology ; Disease Models, Animal ; Endoderm/cytology ; Endoderm/embryology ; Mucous Membrane/cytology ; Mucous Membrane/metabolism ; Xenopus laevis/embryology ; Xenopus laevis/metabolism
    Language English
    Publishing date 2021-01-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2004544-X
    ISSN 1526-968X ; 1526-954X
    ISSN (online) 1526-968X
    ISSN 1526-954X
    DOI 10.1002/dvg.23406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Manipulating and Analyzing Cell Type Composition of the Xenopus Mucociliary Epidermis.

    Walentek, Peter

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1865, Page(s) 251–263

    Abstract: The Xenopus embryonic epidermis serves as a model to investigate the development, cell biology, and regeneration of vertebrate mucociliary epithelia. Its fast development as well as the ease of manipulation and analysis in this system facilitate novel ... ...

    Abstract The Xenopus embryonic epidermis serves as a model to investigate the development, cell biology, and regeneration of vertebrate mucociliary epithelia. Its fast development as well as the ease of manipulation and analysis in this system facilitate novel approaches and sophisticated experiments addressing the principle mechanisms of mucociliary signaling, transcriptional regulation, and morphogenesis. This protocol describes how cell type composition can be manipulated and analyzed, and how mucociliary organoids can be generated and used for "omics"-type of experiments.
    MeSH term(s) Animals ; Cilia/metabolism ; Embryo, Nonmammalian/metabolism ; Epidermis/metabolism ; Molecular Biology/methods ; Mucus/metabolism ; Organoids/metabolism ; Xenopus laevis/embryology ; Xenopus laevis/metabolism
    Language English
    Publishing date 2018-08-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-8784-9_18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Ciliary transcription factors in cancer--how understanding ciliogenesis can promote the detection and prognosis of cancer types.

    Walentek, Peter

    The Journal of pathology

    2016  Volume 239, Issue 1, Page(s) 6–9

    Abstract: Cilia play a plethora of roles in normal development and homeostasis as well as in disease. Their involvement in cell signalling processes and ability to inhibit cell cycle progression make them especially interesting subjects of investigation in the ... ...

    Abstract Cilia play a plethora of roles in normal development and homeostasis as well as in disease. Their involvement in cell signalling processes and ability to inhibit cell cycle progression make them especially interesting subjects of investigation in the context of tumour formation and malignancy. Several key transcription factors regulate the transcriptional programme in cilia formation and some of these, eg RFX factors and FOXJ1, are implicated in cancer formation. Furthermore, RFX factors and FOXJ1 are increasingly being explored for their potential as markers to diagnose, classify and predict the outcome of cancers in patients, including recent work published in this journal on aggressive ependymoma and choroid plexus tumours. Here, some of the key findings and concepts on the roles of ciliary transcription factors in tumourigenesis are highlighted, and a brief perspective is given on how the investigation of ciliogenesis could contribute valuable tools for the diagnosis and prognosis of cancers.
    MeSH term(s) Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Choroid Plexus Neoplasms/metabolism ; Choroid Plexus Neoplasms/pathology ; Ependymoma/metabolism ; Forkhead Transcription Factors/metabolism ; Humans
    Chemical Substances Forkhead Transcription Factors
    Language English
    Publishing date 2016-05
    Publishing country England
    Document type Comment ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3119-7
    ISSN 1096-9896 ; 0022-3417
    ISSN (online) 1096-9896
    ISSN 0022-3417
    DOI 10.1002/path.4703
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Temporal Notch signaling regulates mucociliary cell fates through Hes-mediated competitive de-repression.

    Brislinger-Engelhardt, Magdalena Maria / Lorenz, Fabian / Haas, Maximilian / Bowden, Sarah / Tasca, Alexia / Kreutz, Clemens / Walentek, Peter

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Tissue functions are determined by the types and ratios of cells present, but little is known about self-organizing principles establishing correct cell type compositions. Mucociliary airway clearance relies on the correct balance between secretory and ... ...

    Abstract Tissue functions are determined by the types and ratios of cells present, but little is known about self-organizing principles establishing correct cell type compositions. Mucociliary airway clearance relies on the correct balance between secretory and ciliated cells, which is regulated by Notch signaling across mucociliary systems. Using the airway-like
    Language English
    Publishing date 2023-02-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.15.528675
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The evolutionary history of Brachyury genes in Hydrozoa involves duplications, divergence, and neofunctionalization.

    Vetrova, Alexandra A / Kupaeva, Daria M / Kizenko, Alena / Lebedeva, Tatiana S / Walentek, Peter / Tsikolia, Nikoloz / Kremnyov, Stanislav V

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 9382

    Abstract: Brachyury, a member of T-box gene family, is widely known for its major role in mesoderm specification in bilaterians. It is also present in non-bilaterian metazoans, such as cnidarians, where it acts as a component of an axial patterning system. In this ...

    Abstract Brachyury, a member of T-box gene family, is widely known for its major role in mesoderm specification in bilaterians. It is also present in non-bilaterian metazoans, such as cnidarians, where it acts as a component of an axial patterning system. In this study, we present a phylogenetic analysis of Brachyury genes within phylum Cnidaria, investigate differential expression and address a functional framework of Brachyury paralogs in hydrozoan Dynamena pumila. Our analysis indicates two duplication events of Brachyury within the cnidarian lineage. The first duplication likely appeared in the medusozoan ancestor, resulting in two copies in medusozoans, while the second duplication arose in the hydrozoan ancestor, resulting in three copies in hydrozoans. Brachyury1 and 2 display a conservative expression pattern marking the oral pole of the body axis in D. pumila. On the contrary, Brachyury3 expression was detected in scattered presumably nerve cells of the D. pumila larva. Pharmacological modulations indicated that Brachyury3 is not under regulation of cWnt signaling in contrast to the other two Brachyury genes. Divergence in expression patterns and regulation suggest neofunctionalization of Brachyury3 in hydrozoans.
    MeSH term(s) Animals ; Hydrozoa/genetics ; Phylogeny ; Cnidaria/genetics ; Biological Evolution ; Fetal Proteins/genetics ; Fetal Proteins/metabolism
    Chemical Substances Brachyury protein (EQ43SC3GDB) ; Fetal Proteins
    Language English
    Publishing date 2023-06-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-35979-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Bidirectional multiciliated cell extrusion is controlled by Notch driven basal extrusion and Piezo 1 driven apical extrusion.

    Ventrella, Rosa / Kim, Sun K / Sheridan, Jennifer / Grata, Aline / Bresteau, Enzo / Hassan, Osama / Suva, Eve E / Walentek, Peter / Mitchell, Brian

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Xenopus: Summay statement: Cell extrusion typically occurs unidirectionally. We have identified a single population of multiciliated cells that extrudes bidirectionally: Notch-driven basal extrusion and Piezo 1-mediated apical extrusion. ...

    Abstract Xenopus
    Summay statement: Cell extrusion typically occurs unidirectionally. We have identified a single population of multiciliated cells that extrudes bidirectionally: Notch-driven basal extrusion and Piezo 1-mediated apical extrusion.
    Language English
    Publishing date 2023-01-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.12.523838
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: What we can learn from a tadpole about ciliopathies and airway diseases: Using systems biology in Xenopus to study cilia and mucociliary epithelia.

    Walentek, Peter / Quigley, Ian K

    Genesis (New York, N.Y. : 2000)

    2017  Volume 55, Issue 1-2

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Animals ; Cilia/genetics ; Cilia/pathology ; Ciliopathies/genetics ; Ciliopathies/pathology ; Disease Models, Animal ; Humans ; Larva/growth & development ; Lung Diseases/genetics ; Lung Diseases/pathology ; Mucociliary Clearance/genetics ; Signal Transduction/genetics ; Systems Biology ; Xenopus laevis/genetics
    Language English
    Publishing date 2017-01-17
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2004544-X
    ISSN 1526-968X ; 1526-954X
    ISSN (online) 1526-968X
    ISSN 1526-954X
    DOI 10.1002/dvg.23001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Bidirectional multiciliated cell extrusion is controlled by Notch-driven basal extrusion and Piezo1-driven apical extrusion.

    Ventrella, Rosa / Kim, Sun K / Sheridan, Jennifer / Grata, Aline / Bresteau, Enzo / Hassan, Osama A / Suva, Eve E / Walentek, Peter / Mitchell, Brian J

    Development (Cambridge, England)

    2023  Volume 150, Issue 17

    Abstract: Xenopus embryos are covered with a complex epithelium containing numerous multiciliated cells (MCCs). During late-stage development, there is a dramatic remodeling of the epithelium that involves the complete loss of MCCs. Cell extrusion is a well- ... ...

    Abstract Xenopus embryos are covered with a complex epithelium containing numerous multiciliated cells (MCCs). During late-stage development, there is a dramatic remodeling of the epithelium that involves the complete loss of MCCs. Cell extrusion is a well-characterized process for driving cell loss while maintaining epithelial barrier function. Normal cell extrusion is typically unidirectional, whereas bidirectional extrusion is often associated with disease (e.g. cancer). We describe two distinct mechanisms for MCC extrusion, a basal extrusion driven by Notch signaling and an apical extrusion driven by Piezo1. Early in the process there is a strong bias towards basal extrusion, but as development continues there is a shift towards apical extrusion. Importantly, response to the Notch signal is age dependent and governed by the maintenance of the MCC transcriptional program such that extension of this program is protective against cell loss. In contrast, later apical extrusion is regulated by Piezo1, such that premature activation of Piezo1 leads to early extrusion while blocking Piezo1 leads to MCC maintenance. Distinct mechanisms for MCC loss underlie the importance of their removal during epithelial remodeling.
    MeSH term(s) Animals ; Epithelium ; Signal Transduction ; Xenopus laevis
    Language English
    Publishing date 2023-09-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.201612
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Book ; Online ; Thesis: <dc:title>Loss of cilia in primary ciliated cells and multiciliated cells</dc:title>

    Tasca, Alexia [Verfasser] / Walentek, Peter [Akademischer Betreuer] / Walz, Gerd [Sonstige] / Driever, Wolfgang [Sonstige]

    2023  

    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Universität
    Publishing place Freiburg
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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