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

Abstract

The embryonic skin of Xenopus tadpoles serves as an experimental model system for mucociliary epithelia (MCE) such as the human airway epithelium. MCEs are characterized by the presence of mucus-secreting goblet and multiciliated cells (MCCs). A third cell type, ion-secreting cells (ISCs), is present in the larval skin as well. Synchronized beating of MCC cilia is required for directional transport of mucus. Here we describe a novel cell type in the Xenopus laevis larval epidermis, characterized by serotonin synthesis and secretion. It is termed small secretory cell (SSC). SSCs are detectable at early tadpole stages, unlike MCCs and ISCs, which are specified at early neurulation. Subcellularly, serotonin was found in large, apically localized vesicle-like structures, which were entirely shed into the surrounding medium. Pharmacological inhibition of serotonin synthesis decreased the velocity of cilia-driven fluid flow across the skin epithelium. This effect was mediated by serotonin type 3 receptor (Htr3), which was expressed in ciliated cells. Knockdown of Htr3 compromised flow velocity by reducing the ciliary motility of MCCs. SSCs thus represent a distinct and novel entity of the frog tadpole MCE, required for ciliary beating and mucus transport across the larval skin. The identification and characterization of SSCs consolidates the value of the Xenopus embryonic skin as a model system for human MCEs, which have been known for serotonindependent regulation of ciliary beat frequency.

Control of vertebrate core PCP protein localization and dynamics by Prickle2

“…1C). Comparable asymmetry appeared to occur in other intercalating cell types, such as ionocytes (Dubaissi and Papalopulu, 2011;Quigley et al, 2011) and small secretory cells Walentek et al, 2014), which were identifiable by their significantly smaller surface area and lack of cilia in regions where only intercalating cells had been labeled.…”

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).…”

BMP signalling controls the construction of vertebrate mucociliary epithelia

“…Thus, goblet cells and MCCs are born from lineages that have been separated before the activation of the zygotic genome, which might explain why they respond in an opposite manner to the zygotic inducer BMP. The Xenopus embryonic epidermis also contains ionocytes, which are involved in osmoregulation (Dubaissi and Papalopulu, 2011;Quigley et al, 2011), and SSCs, which control the ciliary beating frequency of MCCs and secrete anti-infective substances that protect the embryo Walentek et al, 2014). Ionocytes and SSCs have no clear counterparts in human airways, so no pertinent comparison can be made.…”

“…In its mature form, the Xenopus embryonic epidermis consists of an epithelial outer layer of goblet cells that is interspersed with MCCs, osmoregulatory ionocytes and serotonin-secreting small secretory cells (SSCs), and an inner layer of non-cohesive P63-positive cells (Deblandre et al, 1999;Dubaissi et al, 2014;Lu et al, 2001;Quigley et al, 2011;Walentek et al, 2014). This tissue emerges from the early non-neural ectoderm in a multistep process.…”