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

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.

A systematic, label-free method for identifying RNA-associated proteinsin vivoprovides insights into vertebrate ciliary beating

“…To test the efficacy of DIF-FRAC on embryonic tissue, we used the pluripotent ectoderm from gastrula stage Xenopus embryos (so-called "animal caps"), which can be readily transformed into a wide array of organs and tissues, including a motile ciliated epithelium (Ariizumi et al, 2009;Walentek and Quigley, 2017;Werner and Mitchell, 2012). This tissue can be obtained in abundance, as we and others have demonstrated in large-scale genomic studies of ciliogenesis and cilia function (Chung et al, 2014;Ma et al, 2014;Quigley and Kintner, 2017).…”

A changing signaling environment induces multiciliated cell trans-differentiation during developmental remodeling

“…Like the mammalian airway epithelium, the Xenopus embryonic epidermis is composed of MCCs, ionocytes, mucus-secreting cells (Goblet and SSCs), and subepithelial basal stem cells (Haas et al, 2019;Walentek and Quigley, 2017). Once established by stage (st.) 32, cell type composition is generally invariable between individuals (Haas et al, 2019).…”

“…Hence, it is widely considered impossible for MCCs to undergo fate change during normal development and in regeneration. In mucociliary epithelia, such as the airway epithelium or the embryonic epidermis of Xenopus tadpoles, correct balance between MCCs and secretory cells provides the functional basis for removal of particles and pathogens to prevent infections and to maintain organismal oxygenation (Walentek and Quigley, 2017). Mucociliary epithelial remodeling and MCC loss are observed in human chronic lung disease as well as during metamorphosis in Xenopus, however, it remains unresolved how and why MCCs are lost in various conditions (Hogan et al, 2014).…”

Tissue mechanics drives epithelialization, goblet cell regeneration, and restoration of a mucociliated epidermis on the surface of embryonic aggregates

“…Xenopus embryos develop a mucociliary epidermis that functions much like respiratory epithelia in mammals 1,2 . Goblet cell progenitors develop exclusively from the epithelial surface layer whereas multiciliated and other accessory cells derive from deeper layer cells [3][4][5][6] following notch-mediated patterning 7 .…”