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      Formation and function of multiciliated cells

      review-article
      1 , 1 , 1 , 2 , , 1 ,
      The Journal of Cell Biology
      Rockefeller University Press

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          Abstract

          Lyu et al. summarize the current knowledge of multiciliogenesis by which the respiratory tract, brain ventricles, and reproductive tracts of vertebrates form multiple motile cilia for tissue homeostasis.

          Abstract

          In vertebrates, multiciliated cells (MCCs) are terminally differentiated cells that line the airway tracts, brain ventricles, and reproductive ducts. Each MCC contains dozens to hundreds of motile cilia that beat in a synchronized manner to drive fluid flow across epithelia, the dysfunction of which is associated with a group of human diseases referred to as motile ciliopathies, such as primary cilia dyskinesia. Given the dynamic and complex process of multiciliogenesis, the biological events essential for forming multiple motile cilia are comparatively unelucidated. Thanks to advancements in genetic tools, omics technologies, and structural biology, significant progress has been achieved in the past decade in understanding the molecular mechanism underlying the regulation of multiple motile cilia formation. In this review, we discuss recent studies with ex vivo culture MCC and animal models, summarize current knowledge of multiciliogenesis, and particularly highlight recent advances and their implications.

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          Basal cells as stem cells of the mouse trachea and human airway epithelium.

          The pseudostratified epithelium of the mouse trachea and human airways contains a population of basal cells expressing Trp-63 (p63) and cytokeratins 5 (Krt5) and Krt14. Using a KRT5-CreER(T2) transgenic mouse line for lineage tracing, we show that basal cells generate differentiated cells during postnatal growth and in the adult during both steady state and epithelial repair. We have fractionated mouse basal cells by FACS and identified 627 genes preferentially expressed in a basal subpopulation vs. non-BCs. Analysis reveals potential mechanisms regulating basal cells and allows comparison with other epithelial stem cells. To study basal cell behaviors, we describe a simple in vitro clonal sphere-forming assay in which mouse basal cells self-renew and generate luminal cells, including differentiated ciliated cells, in the absence of stroma. The transcriptional profile identified 2 cell-surface markers, ITGA6 and NGFR, which can be used in combination to purify human lung basal cells by FACS. Like those from the mouse trachea, human airway basal cells both self-renew and generate luminal daughters in the sphere-forming assay.
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            p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development.

            The p63 gene, a homologue of the tumour-suppressor p53, is highly expressed in the basal or progenitor layers of many epithelial tissues. Here we report that mice homozygous for a disrupted p63 gene have major defects in their limb, craniofacial and epithelial development. p63 is expressed in the ectodermal surfaces of the limb buds, branchial arches and epidermal appendages, which are all sites of reciprocal signalling that direct morphogenetic patterning of the underlying mesoderm. The limb truncations are due to a failure to maintain the apical ectodermal ridge, a stratified epithelium, essential for limb development. The embryonic epidermis of p63-/- mice undergoes an unusual process of non-regenerative differentiation, culminating in a striking absence of all squamous epithelia and their derivatives, including mammary, lacrymal and salivary glands. Taken together, our results indicate that p63 is critical for maintaining the progenitor-cell populations that are necessary to sustain epithelial development and morphogenesis.
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              Centrioles, centrosomes, and cilia in health and disease.

              Centrioles are barrel-shaped structures that are essential for the formation of centrosomes, cilia, and flagella. Here we review recent advances in our understanding of the function and biogenesis of these organelles, and we emphasize their connection to human disease. Deregulation of centrosome numbers has long been proposed to contribute to genome instability and tumor formation, whereas mutations in centrosomal proteins have recently been genetically linked to microcephaly and dwarfism. Finally, structural or functional centriole aberrations contribute to ciliopathies, a variety of complex diseases that stem from the absence or dysfunction of cilia.
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                Author and article information

                Contributors
                Role: Writing - original draftRole: Writing - review & editing
                Role: Funding acquisitionRole: VisualizationRole: Writing - review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing - review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing - original draftRole: Writing - review & editing
                Journal
                J Cell Biol
                J Cell Biol
                jcb
                The Journal of Cell Biology
                Rockefeller University Press
                0021-9525
                1540-8140
                01 January 2024
                30 November 2023
                30 November 2023
                : 223
                : 1
                : e202307150
                Affiliations
                [1 ]Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University ( https://ror.org/01wy3h363) , Jinan, China
                [2 ]State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University; , Tianjin, China
                Author notes
                Correspondence to Huijie Zhao: zhaohuijie@ 123456sdnu.edu.cn
                [*]

                Q. Lyu and Q. Li contributed equally to this paper.

                Disclosures: The authors declare no competing interests exist.

                Author information
                https://orcid.org/0009-0002-0198-6433
                https://orcid.org/0000-0002-0307-0085
                https://orcid.org/0000-0003-3131-7804
                https://orcid.org/0000-0002-8595-8159
                Article
                jcb.202307150
                10.1083/jcb.202307150
                10689204
                38032388
                0ef3204b-35d5-4199-ae75-955883369a29
                © 2023 Lyu et al.

                This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

                History
                : 31 July 2023
                : 29 October 2023
                : 14 November 2023
                Funding
                Funded by: National Natural Science Foundation of China, DOI http://dx.doi.org/10.13039/100014717;
                Award ID: 32270807
                Award ID: 31900538
                Award ID: 31991193
                Funded by: Shandong Natural Science Foundation, DOI http://dx.doi.org/10.13039/501100007129;
                Award ID: 2022HWYQ-075
                Categories
                Review
                Development
                Cilia

                Cell biology
                Cell biology

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