Trends in Genetics
Volume 19, Issue 3, March 2003, Pages 162-167
Journal home page for Trends in Genetics

Lateralization defects and ciliary dyskinesia: lessons from algae

https://doi.org/10.1016/S0168-9525(03)00026-XGet rights and content

Abstract

Flagella and cilia are two very similar organelles that ‘beat’ to move cells and to propel fluid over tissues. They are highly conserved, being found in organisms ranging from prokaryotes to plant and animal eukaryotes. In humans, cilia are present in almost every organ, and several human conditions involve dysfunctional cilia; for example, lateralization defects, where the positions of organs are reversed, and primary ciliary dyskinesia, a rare condition where patients suffer from recurrent respiratory infections. In this article, we will discuss how information gained from studies on algae has aided research into these human diseases. These studies found a variety of functions that was previously unsuspected, renewing interest in cilia.

Section snippets

Structure of flagella and cilia

The structure of cilia and flagella is similar in Chlamydomonas and humans 1, 10 (Fig. 2). Both organelles protrude from the cells and contain a highly organized scaffold of molecules called the axoneme. Usually, the axoneme is formed from ten pairs of microtubules, with nine peripheral pairs arranged around a central pair (i.e. a 9+2 formation; Fig. 2a). The peripheral pairs are each composed of a complete tubule (A) fused to a partial tubule (B). The central pair of microtubules are termed C1

Dynein arms

At least 28 Chlamydomonas mutants with different dynein arm anomalies have been characterized [10]. Mutations in the dynein IC78 of Chlamydomonas cause slow-swimming mutants with ultrastructural defects of the ODA [11]. Cloning of the orthologous human gene, DNAI1 (DN for dynein, A for axonemal and I for intermediate chain), showed that it is mutated in several, but not all, patients with PCD 12, 13. ODAs were absent from the five reported PCD patients carrying DNAI1 mutations, indicating that

Establishment of left–right asymmetry and the role of cilia

An important question that has recently received an answer concerns the relationship between ciliary function and body lateralization: why do half of PCD patients present with situs inversus?

The looping of the primitive heart tube to the right is the first evidence of lateralization in the embryo. It is thought that lateralization occurs in four steps: (1) initial breaking of bilateral symmetry; (2) establishment of asymmetric gene expression patterns within the embryonic organizer (the mouse

Left–right defects

Any type of disturbance of left–right polarity is termed collectively lateralization defect (LD) or heterotaxy. The incidence of LD is roughly 1 in 8000 births. A person with situs inversus and no other anomaly is symptom free. However, anomalies such as midline defects or ciliary dyskinesia that might be associated with situs inversus do cause symptoms. Furthermore, complications are frequent in incomplete left–right reversal (situs ambiguus). In situs ambiguus, the normal cardiac architecture

Conclusion

The molecular mechanisms controlling the normal growth and function of Chlamydomonas arms have obvious implications for the understanding of cilia and flagella in vertebrates. However, the kinetics of Chlamydomonas arms differ from vertebrate cilia and flagella. Moreover, these organelles in vertebrates have beating patterns that vary among tissues, and some cilia are immotile (e.g. monocilia of kidney epithelial cells). This versatility suggests that beside basic components, there are proteins

Acknowledgements

We thank Heidi Felix for electron microscopy; Bjorn Afzelius and the reviewers for their help in improving the manuscript; Mark Jorissen and Tom Willems for providing us with a picture of human respiratory epithelial cells in culture; and Julien Bouvagnet for his help in preparing the figures.

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