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.
KeywordsCilia; Left-Right; Kidney; Zebrafish; Medaka; Xenopus; Kidney; PKD; ADPKD; ARPKD; NPHP; BBS; Review
INTRODUCTIONFlagella were initially described as a cellular organelle in Chlamydomonas and subsequently shown to be homologues to cilia present in most vertebrate cell types (1). Cilia are membrane extensions contiguous with the cell membrane characterized by the presence of nine peripheral doublets of microtubules. Most motile cilia also contain a central microtubule pair (9+2 pattern), while primary, sensory cilia lack this microtubule axoneme at its center and are referred to as 9+0 pattern. As first discovered in Chlamydomonas flagella (and cilia) are assembled by a process called intraflagella transport (IFT), in which large protein particles are carried along the ciliary microtubules by kinesin and dynein (2,3). Studies in Chlamydomonas demonstrated that IFT particles are transport vehicles necessary for assembly, maintenance and function of flagella (4). Since then, IFT homologues have been identified in many different animal model systems, including C. elegans, Drosophila, zebrafish, medaka, Xenopus and mammals (5,6,7,8) and mutations in the IFT genes showed that they are required for cilia assembly in Chlamydomonas (9), C. elegans (10, 11, (13,14,15,16). Interestingly, those studies not only show that IFTs are required for the structural integrity of cilia, but also implicated cilia as a possible common mechanism underlying several human pathologies, including left-right asymmetry defects, polycystic kidney disease, and retinal degeneration. Furthermore, recent studies suggest that the cilium participates in signal transduction pathways such as Hedgehog, Ca 2+ , Wnt, STATs, controlling cell proliferation and differentiation. There are many excellent, recent reviews discussing the role of cilia in those individual scenarios (17,18,19,20,21,22,23,24). This review will summarize how the study of ciliogenesis has contributed to a better understanding of embryonic development in the lower, non...