Multiciliated cells

Abstract

Cilia are microtubule-based projections that serve a wide variety of essential functions in animal cells. Defects in cilia structure or function have recently been found to underlie diverse human diseases. While many eukaryotic cells possess only one or two cilia, some cells, including those of many unicellular organisms, exhibit many cilia. In vertebrates, multiciliated cells are a specialized population of post-mitotic cells decorated with dozens of motile cilia that beat in a polarized and synchronized fashion to drive directed fluid flow across an epithelium. Dysfunction of human multiciliated cells is associated with diseases of the brain, airway and reproductive tracts. Despite their importance, multiciliated cells are relatively poorly studied and we are only beginning to understand the mechanisms underlying their development and function. Here, we review the general phylogeny and physiology of multiciliation and detail our current understanding of the developmental and cellular events underlying the specification, differentiation and function of multiciliated cells in vertebrates.

Figure 1. Examples of vertebrate MCCs

(a) Ependymal MCCs stained for acetylated tubulin in green and beta-catenin in magenta. Note the unipolar clustering of axonemes within each cell. Image courtesy of Shinya Ohata and Arturo Alvarez-Buylla. (b) SEM of a mouse tracheal epithelial MCC. Image courtesy of Eszter Vladar and Jeff Axelrod. (c) A Xenopus epidermal MCC expressing GFP-MAP7 and RFP-CLAMP to label the proximal and distal axoneme respectively.

Figure 2. Overview of selected MCC populations

This figure shows the organismal context and morphology of some MCC populations, from unicellular organisms to specialized vertebrate tissues.

Figure 3. Schematic of metachronal organization

Multiciliated cells often exhibit a specialized synchronization known as metachrony, which results in a traveling wave of coordinated ciliary organization across the surface of the cell. Here an array of axonemes is shown at a single time point. Note that axonemes are phase-shifted with respect to their neighbors along the axis of the effective stroke (the metachronal axis) but are in synchrony with neighbors along the perpendicular axis.

Figure 4. Transcriptional controls of multiciliogenesis

The transcriptional cascade leading to the generation of MCC axonemal tufts is outlined for mucocilairy MCCs (i.e. the mammalian airway and the Xenopus epidermis) and for ependymal MCCs. Solid lines represent direct interactions, dashed lines represent indirect (or unknown) interactions. Selected known target genes are written in italics, and labeled with the color of the transcription factor controlling them. Asterisk indicates that connection is only known for mucuociliary cells.

Figure 5. A schematic representation of de novo basal body biogenesis