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

Abstract

The larval epidermis of Xenopus is a bilayered epithelium, which is an excellent model system for the study of the development and function of mucosal and mucociliary epithelia. Goblet cells develop in the outer layer while multiciliated cells and ionocytes sequentially intercalate from the inner to the outer layer. Here, we identify and characterise a fourth cell type, the small secretory cell (SSC). We show that the development of these cells is controlled by the transcription factor Foxa1 and that they intercalate into the outer layer of the epidermis relatively late, at the same time as embryonic hatching. Ultrastructural and molecular characterisation shows that these cells have an abundance of large apical secretory vesicles, which contain highly glycosylated material, positive for binding of the lectin, peanut agglutinin, and an antibody to the carbohydrate epitope, HNK-1. By specifically depleting SSCs, we show that these cells are crucial for protecting the embryo against bacterial infection. Mass spectrometry studies show that SSCs secrete a glycoprotein similar to Otogelin, which may form the structural component of a mucus-like protective layer, over the surface of the embryo, and several potential antimicrobial substances. Our study completes the characterisation of all the epidermal cell types in the early tadpole epidermis and reinforces the suitability of this system for the in vivo study of complex epithelia, including investigation of innate immune defences.

A novel serotonin-secreting cell type regulates ciliary motility in the mucociliary epidermis of Xenopus tadpoles

“…The accompanying manuscript by Dubaissi et al describes SSCs in the epidermis of Xenopus tropicalis and demonstrates their specification by the forkhead transcription factor foxa1 (Dubaissi et al, 2014). The colocalization of peanut agglutinin and serotonin in both species clearly demonstrates that the identical cell type was characterized in these studies.…”

“…They are characterized by small cell size and apical release of serotonincontaining vesicles, which clearly distinguishes them from goblet or ion-secreting cells (Dubaissi and Papalopulu, 2011;Hayes et al, 2007;Montorzi et al, 2000;Quigley et al, 2011). In the accompanying paper, Papalopulu and colleagues have independently identified and characterized a novel small secretory cell type in the embryonic skin of Xenopus tropicalis (Dubaissi et al, 2014). They used fluorescently labeled peanut agglutinin (PNA) to identify these cells.…”

“…MCCs and ISCs arise from the deep ectodermal layer that contains a pool of precursor cells (Dubaissi and Papalopulu, 2011;Quigley et al, 2011;Stubbs et al, 2006), which are specified much earlier than SSCs (neurula versus early tadpole stages, respectively). The accompanying paper by Dubaissi and colleagues, however, shows that SSCs intercalate into the superficial epidermal cell layer as well, which is paralleled by the appearance of multiple serotonin containing vesicle-like structures (Dubaissi et al, 2014). During further development, vesicles progressively localize to the apical surface and get released in due course.…”

“…The colocalization of peanut agglutinin and serotonin in both species clearly demonstrates that the identical cell type was characterized in these studies. Additional common characteristics comprise the presence of large vesicles as well as embryonic death upon serotonin depletion (not shown) or foxa1 knockdown (Dubaissi et al, 2014). Intriguingly, Xenopus tropicalis SSCs release mucuslike substances, physically protecting the epidermis against bacterial infections (Dubaissi et al, 2014).…”

ERK7 regulates ciliogenesis by phosphorylating the actin regulator CapZIP in cooperation with Dishevelled

“…1c). In the Xenopus epidermis, four types of cells, alpha-ionocytes, betaionocytes, small secretory cells and MCCs, are distributed in a salt-and-pepper pattern [14][15][16][17][18][19] . MCCs bear many cilia on their surface, and therefore, they can be detected by immunostaining with an antibody against acetylated a-tubulin (a marker of cilia).…”