Fish and frogs: models for vertebrate cilia signaling

Abstract

The presence of cilia in many vertebrate cell types and its function has been ignored for many years. Only in the past few years has its importance been rediscovered. In part, this was triggered by the realization that many gene products mutated in polycystic kidney diseases are localized to cilia and dysfunctional cilia result in kidney disease. Another breakthrough was the observation that the establishment of the left-right body axis is dependent on cilia function. Since then, many other developmental paradigms have been shown to rely on cilia-dependent signaling. In addition to mouse and Chlamydomonas, lower vertebrate model systems such as zebrafish, medaka and Xenopus have provided important new insights into cilia signaling and its role during embryonic development. This review will summarize those studies. We will also illustrate how these lower vertebrates are promising model systems for future studies defining the physiological function of cilia during organogenesis and disease pathophysiology.

Figure 1

Adult see-through medaka fish. The left (A) and right (B) sides of the body of a female. The dorsal (C) and ventral (D) views of a male. a, air bladder; b, brain; bv, blood vessels; c, conjunctiva; f, fat tissue; g, gill; gu, gut; h, heart; k, kidney; 1, lens; li, liver; o, ovary; oc, optic cup; s, spleen; sc, spinal cord. The dark color of the gut comes from ingested feed (the scale bar represents 4 mm.). Reproduced with permission from Y. Wakamatsu (38) and PNAS Copyright (2001) National Academy of Sciences, U.S.A..

Figure 2

Schematic diagram of the zebrafish/medaka (A) and the Xenopus (B) pronephros. Note that multiciliated cells are present in a salt-and-pepper fashion in teleosts, while they are restricted to the nephrostomes in amphibians.

Figure 3

Scanning electron microscopy picture of a pronephric tubule section of medaka. The cell borders are indicated by arrowheads; mc, multi-ciliated cell; br, brush border. Reproduced with permission from Y. Wakamatsu (39) and Nature publishing group.

Figure 4

Enhanced ciliogenesis and double bubble-mutant rescue by inhibition of Jagged/Notch signaling. (A) dbb-mutant homozygote at 2.5 dpf showing bilateral cyst formation in the proximal pronephros (arrow). (B) dbb-mutant homozygote injected with jagged 2 exon 20 MO at the one-cell stage, showing the absence of cyst formation (arrow; mutant rescue). (C) Histological section of dbb-homozygote pronephros showing a cystic pronephric tubule (*), dilated pronephric tubules (arrow) and edema (#). (D) Histological section of a dbb homozygote injected with jagged 2 exon 20 MO at the one-cell stage, showing complete absence of cystic pathology and edema (arrow, wild-type-appearing pronephric tubules; *, normal glomerular structure). Reproduced with permission from I. A. Drummond (79) and the Company of Biologists Ltd.