Notch signaling induces either apoptosis or cell fate change in multiciliated cells during mucociliary tissue remodeling

Tasca, Alexia; Helmstädter, Martin; Brislinger, Magdalena; Haas, Maximilian; Mitchell, Brian J.; Walentek, Peter

doi:10.1016/j.devcel.2020.12.005

Cited by 32 publications

(42 citation statements)

References 59 publications

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“…Overall, our findings reveal that the differentiation of agr2 + EMCs is controlled by Delta/Jagged ligand induction of Notch signaling. This result is consistent with a recent publication that showed Notch signaling induces a secretory cell fate change in epidermal multiciliated cells of Xenopus embryos [ 39 ]. Thus, our results suggest that the specification of three major cell types in the epidermis depends on temporally distinct Notch-dependent signaling events, and this consistent involvement of Notch signaling in epidermal cell development may be common to many vertebrate species.…”

Section: Discussionsupporting

confidence: 94%

Delta/Jagged-mediated Notch signaling induces the differentiation of agr2-positive epidermal mucous cells in zebrafish embryos

Liu

et al. 2021

PLoS Genet

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Teleosts live in aquatic habitats, where they encounter ionic and acid-base fluctuations as well as infectious pathogens. To protect from these external challenges, the teleost epidermis is composed of living cells, including keratinocytes and ionocytes that maintain body fluid ionic homeostasis, and mucous cells that secret mucus. While ionocyte progenitors are known to be specified by Delta-Notch-mediated lateral inhibition during late gastrulation and early segmentation, it remains unclear how epidermal mucous cells (EMCs) are differentiated and maintained. Here, we show that Delta/Jagged-mediated activation of Notch signaling induces the differentiation of agr2-positive (agr2+) EMCs in zebrafish embryos during segmentation. We demonstrated that agr2+ EMCs contain cytoplasmic secretory granules and express muc5.1 and muc5.2. Reductions in agr2+ EMC number were observed in mib mutants and notch3 MOs-injected notch1a mutants, while increases in agr2+ cell number were detected in notch1a- and X-Su(H)/ANK-overexpressing embryos. Treatment with γ-secretase inhibitors further revealed that Notch signaling is required during bud to 15 hpf for the differentiation of agr2+ EMCs. Increased agr2+ EMC numbers were also observed in jag1a-, jag1b-, jag2a- and dlc-overexpressing, but not jag2b-overexpressing embryos. Meanwhile, reductions in agr2+ EMC numbers were detected in jag1a morphants, jag1b mutants, jag2a mutants and dlc morphants, but not jag2b mutants. Reduced numbers of pvalb8-positive epidermal cells were also observed in mib or jag2a mutants and jag1a or jag1b morphants, while increased pvalb8-positive epidermal cell numbers were detected in notch1a-overexpressing, but not dlc-overexpressing embryos. BrdU labeling further revealed that the agr2+ EMC population is maintained by proliferation. Cell lineage experiments showed that agr2+ EMCs are derived from the same ectodermal precursors as keratinocytes or ionocytes. Together, our results indicate that specification of agr2+ EMCs in zebrafish embryos is induced by DeltaC/Jagged-dependent activation of Notch1a/3 signaling, and the cell population is maintained by proliferation.

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Section: Discussionsupporting

confidence: 94%

Delta/Jagged-mediated Notch signaling induces the differentiation of agr2-positive epidermal mucous cells in zebrafish embryos

Liu

et al. 2021

PLoS Genet

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“…Thus, unlike in airways, the mucus on the frog embryonic skin may not be propelled as a coherent layer, which would explain the much lower density of MCCs necessary in this system. Although additional functions, such as oxygenation of the skin, are not ruled out, our proposed pathogen clearance function is consistent with the resorption of MCCs in pre-metamorphic tadpoles (Tasca et al, 2020), at a stage when innate immunity is in place (Robert and Ohta, 2009).…”

Section: Discussionsupporting

confidence: 72%

Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function

Nommick

Boutin

Rosnet

et al. 2022

Journal of Cell Science

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Ciliated epithelia perform essential functions across animal evolution, ranging from locomotion of marine organisms to mucociliary clearance of airways in mammals. These epithelia are composed of multiciliated cells (MCCs) harbouring myriads of motile cilia, which rest on modified centrioles called basal bodies (BBs), and beat coordinately to generate directed fluid flows. Thus, BB biogenesis and organization is central to MCC function. In basal eukaryotes, the coiled-coil domain proteins Lrrcc1 and Ccdc61 were shown to be required for proper BB construction and function. Here, we used the Xenopus embryonic ciliated epidermis to characterize Lrrcc1 and Ccdc61 in vertebrate MCCs. We found that they both encode BB components, localized proximally at the junction with striated rootlets. Knocking down either gene caused defects in BB docking, spacing, and polarization. Moreover, their depletion impaired the apical cytoskeleton, and altered ciliary beating. Consequently, cilia-powered fluid flow was greatly reduced in morphant tadpoles, which displayed enhanced mortality when exposed to pathogenic bacteria. This work illustrates how integration across organizational scales make elementary BB components essential for the emergence of the physiological function of ciliated epithelia.

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“…Amphibian metamorphosis involves numerous, precisely timed developmental changes, including intestinal remodeling, limb growth, vascular reorganization, changes to the neuronal circuitry, tail resorption, simultaneous gill resorption and lung maturation, and the change from ciliated larval epidermis to adult skin ( Brown and Cai, 2007 ; Choi et al, 2017 ; Tasca et al, 2021 ). The three phases of metamorphosis (premetamorphosis, prometamorphosis and climax metamorphosis) are represented by NF stages 48-59 ( Figs 8 A,B, 9 and 10 A), NF stage 63 (tailed froglet; Fig.…”

Section: Resource Descriptionmentioning

confidence: 99%

Normal Table of Xenopus development: a new graphical resource

Zahn¹,

James-Zorn

Ponferrada

et al. 2022

Development

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Normal tables of development are essential for studies of embryogenesis, serving as an important resource for model organisms, including the frog Xenopus laevis. Xenopus has long been used to study developmental and cell biology, and is an increasingly important model for human birth defects and disease, genomics, proteomics and toxicology. Scientists utilize Nieuwkoop and Faber's classic ‘Normal Table of Xenopus laevis (Daudin)’ and accompanying illustrations to enable experimental reproducibility and reuse the illustrations in new publications and teaching. However, it is no longer possible to obtain permission for these copyrighted illustrations. We present 133 new, high-quality illustrations of X. laevis development from fertilization to metamorphosis, with additional views that were not available in the original collection. All the images are available on Xenbase, the Xenopus knowledgebase (http://www.xenbase.org/entry/zahn.do), for download and reuse under an attributable, non-commercial creative commons license. Additionally, we have compiled a ‘Landmarks Table’ of key morphological features and marker gene expression that can be used to distinguish stages quickly and reliably (https://www.xenbase.org/entry/landmarks-table.do). This new open-access resource will facilitate Xenopus research and teaching in the decades to come.

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Notch signaling induces either apoptosis or cell fate change in multiciliated cells during mucociliary tissue remodeling

Cited by 32 publications

References 59 publications

Delta/Jagged-mediated Notch signaling induces the differentiation of agr2-positive epidermal mucous cells in zebrafish embryos

Delta/Jagged-mediated Notch signaling induces the differentiation of agr2-positive epidermal mucous cells in zebrafish embryos

Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function

Normal Table of Xenopus development: a new graphical resource

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