Aquatic models of human ciliary diseases

Abstract

Cilia are microtubule-based structures that either transmit information into the cell or move fluid outside of the cell. There are many human diseases that arise from malfunctioning cilia. Although mammalian models provide vital insights into the underlying pathology of these diseases, aquatic organisms such as Xenopus and zebrafish provide valuable tools to help screen and dissect out the underlying causes of these diseases. In this review we focus on recent studies that identify or describe different types of human ciliopathies and outline how aquatic organisms have aided our understanding of these diseases.

Keywords: Xenopus; cilia; ciliopathy; cystic kidney; kidney; nasal; node; zebrafish.

Figure 1:

Structure of cilia. The cilia are composed of three main sections, the axoneme which performs the sensory or movement function, the transition zone which likely contains over 100 proteins which function to anchor the cilia and regulate transport to and from the cilia, and the basal body which is a centriole that functions as a tubulin organizing center to form the cilia. Diagram showing the cross section of the axoneme of common types of motile and primary cilia in vertebrates.

Figure 2:

Confocal images of wholemount zebrafish (3dpf) and Xenopus laevis (Stage 37) kidney cilia. Cilia were stained using an acetylated alpha-tubulin antibody (Sigma T6793) which labels the neurons and cilia. Kidney cilia are pseudocolored in green while neurons and epithelial cilia are pseudocolored in red. The zebrafish and Xenopus kidney are outlined in white dashed lines, and motile multiciliated cells in the kidney are pseudocolored in magenta. Images were taken on a Zeiss LSM800 confocal microscope.

Figure 3:

Images of Xenopus laevis motile epidermal cilia. A-C) Confocal imaging of acetylated alpha-tubulin stained whole mount Xenopus embryo. D-E) Scanning electron micrograph of the skin of whole mount Xenopus embryo. E-F) Transmission electron microscopy showing sections through cilia. F) Image showing basal body and axoneme of motile cilia G.) Image showing cross-section and the 9+2 microtubule structure of motile cilia. C,E) Zoomed in image of white dashed box in B and D.

Figure 4:

Confocal images of the motile cilia lining the zebrafish nasal (olfactory) pit. Dorsal view of 8dpf zebrafish embryos with head towards the top of the image. Embryos were fixed and stained with acetylated alpha-tubulin (Green) (Sigma T6793) and DAPI (Blue). Acetylated tubulin labels both the cilia and neurons. Nasal pits are circled in white, and neural mast cells are circled in red.

Figure 5:

Diagram of a posterior view of the Left-Right organizer and its functions. Motile cilia (green) create a leftward flow of fluid over the cleft. This leftward flow activated primary cilia (red) on the left half of the cleft resulting in the opening of polycystin calcium channels. Calcium influx inhibits a protein Coco leading to activation of Nodal signaling.