Cilia - the prodigal organelle

Article (PDF Available)inCilia 1(1):1 · April 2012with19 Reads
DOI: 10.1186/2046-2530-1-1 · Source: PubMed

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EDI T O R I A L Open Access
Cilia - the prodigal organelle
Phil Beales
1*
and Peter K Jackson
2
Cilia are the oldest known cellular organelle , first
described in 1675 by Anthony van Leeuwenhoek in proto-
zoa [1]. He described them as incredibly thin feet, or little
legs, which were moved very nimbly.Thetermcilium
(Latin for eyelash) was probably first coined by Otto Mul-
ler in 1786 [2]. Structurally and functionally similar to
eukaryotic flagella, cilia were originally defined by their
motility and for many decades this was their only ascribed
purpose. During the latter half of the 19th century came
the observation of another class of solitary cilium, which
for the most-part was non-motile [3-5]. Zimmerman, who
first described centralgeissel (central flagella) in mamma-
lian cells also proposed a sensory role for them, but they
received little attention thereafter [5]. The organelle was
renamed primary cilia in 1968 [6] because the primary
cilium was noted to appear first before multiciliat ed cells
appear in the central nervous system. But their function
remained elusive until this past decade. In fact, the revela-
tion that primary cilia have a sensory role, signalling to the
cell interior external cues which underlie many human
diseases, has somewhat eclipsed research into motile cilia.
This split with two cilia categories is however, short lived
as more recent evidence indicates that, as long suspected,
motile cilia/flagella also have sensory potential (see [7] for
a review).
So why establish a journal devoted to this once forgot-
ten organelle? The reasons are simple: interest and
importance. In 1997-1998 there were a handful of publi-
cations citing work on prima ry cilia with the main focus
on olfactory receptors (Figure 1). That year howe ver, saw
the publication of Nonaka and Hirokawas seminal paper
on nodal cilia and left-right asymmetry which helped
kick-start the field [8]. The year 1998 also produced the
classic purification of the intraflagellar transport (IFT)
complexes from Cole and Rosenbaum [9], providing the
molecular basis for previous discovery from Koszminski
and Rosenbaum of the intraflagellar transport process
[10]. This led in rapid succession to links between poly-
cystic kidney disease and cilia , starting with the link o f
C. elegans homolog of the PKD1 and PKD2 polycystins,
mutated in human polycystic kidney disease, to sensory
cilia [11]; the link of IFT-B components to mutations in
left-right asymmetry [12]; and the link between the IFT-
B complex, the polycystic kidney disease gene tg737 and
ciliary assembly [13]. In 2003, work from Kathryn Ander-
sons lab made the striking connection between primary
cilia and Hedgehog signaling [14], which caught the
attention of developmental biologists a nd helped bring
cilia into the mainstream of developmental cell biology.
A variety of links between cilia and morphogen pathways
have since been p ublished, causing both enthusiasm and
controversy. The year 2006 saw a 20-fold increase in
publications on the topic with an emphasis on the role of
cilia in polycystic kidney disease. Since 2007, a growing
number of publications have characterized interacting
networks of proteins that form cr itical parts of the ciliary
trafficking and signaling machinery, and linked these net-
works and co mplexes to the human genetic disease, pro-
viding deeper explanations for human genetic diseases
like Bardet-Biedl syndrome, nephronophthisis, Joubert,
and Meckel-Gruber syndromes. Publicati ons in 2011
continued to report a plethora of inherited diseases
linked to cilia dysfunction and mechanisms governing
trafficking to and within the cilium. Within little over a
decade, a new field of biomedical research was born out
of observations of this forgotten organelle. This interest
will continue unabated for the foreseeable future as new
and exciting cellular, developmental and disease-related
revelations are made.
It has emerged that the cilium should not be viewed in
isolation but rather as intrinsically linked to other orga-
nelles - the basal body, centroso me, actin, and microtub-
ular cytoskeleton; to other cellular processes - cell cycle,
division, and cytokinesis; and to other signaling pathways
important for development: Hedgehog, Wnt, Notch. We
are mindful of the need to maintain flexibility and
breadth in the types of manuscripts that will be consid-
ered fo r publication in Cilia. As reflected in the launch
edition, we welcome papers covering the function of the
centrosome, as well as aspects of the cytoskeleton of
interest to cilia biologists. We are especially interested in
* Correspondence: p.beales@ucl.ac.uk
1
UCL Institute of Child Health, London WC1N 1EH, UK
Full list of author information is available at the end of the article
Beales and Jackson Cilia 2012, 1:1
http://www.ciliajournal.com/content/1/1/1
© 2012 Beales and Jackson; licensee BioMed Central Ltd. This is an open access articl e distributed under the te rms of the Creative
Commons Attribution License (http://creativecommons.org/license s/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provi ded the original work is properly cited.
articles that help explain links between cilia and disease
process. There is a great opportunity to not only connect
cilia to human genetic diseases ( ciliopathies ), but to
explain the role of ciliary sig naling in normal physiology
and potentially to link cilia to disease pathologies that are
not clearly genetic in nature. To date, we know little
about the role that cilia may play in metabolic disease,
infectious disease, and only a glimmer of what the role of
cilia in cancer may be.
Cilia expects to publish a wide range of topics from
the structure of cilia to human genetics to ciliotherapeu-
tics and our expectation is that the journalsstructure
will evolve. This should not be a problem for an online
journal. We ex pect to publish both full research articles
and shorter reports. These reports might range from a
collection of clinical observations on a ciliary dise ase, to
a human genetics analysis of mutations in a disease
cluster, to an omics analysis of some ciliary regulators,
and t o detailed microscopy revealing a new structure.
The reports need not be long, even one figure could be
considered. They only need be of immediate interest to
our community of cilia biologists, and to have data of
high quality. We also welcome solicitations for reviews
or opinion pieces. We are committed to a rapid and fair
review of papers.
Of paramount importance to both of us as editors is
the fact that Cilia is an open access title and we are
grateful to BioMed Central for their commitment to sup-
port its launch and maintain its profile. We have been
delighted by the enthusiastic response of the contributing
authors whose works are showcased in this first edition.
Author details
1
UCL Institute of Child Health, London WC1N 1EH, UK.
2
Genentech Inc.,
South San Francisco, CA 94080, USA.
Received: 12 April 2012 Accepted: 25 April 2012
Published: 25 April 2012
References
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Brace and Co, New York; 1932.
2. Muller OF: Animalcula infusoria; fluvia tilia et marina, que detexit, systematice
descripsit et ad vivum delineari curavit. Typis N. Molleri, Havniae 1786.
3. Kowalevsky A: Entwickelungsgeschichte des Amphioxus lanceolatus.
Memoires de lAcademie Imperiale des Sciences de St-Petersbourg VII 1867,
11:1-17.
4. Langerhans P: Zur Anatomie des Amphioxus. 1876, 12:290-348.
5. Zimmermann KW: Beitrage zur Kenntniss einiger Drusen und Epithelien.
Arch Mikrosk Anat 1898, 52:552-706.
6. Sorokin SP: Reconstructions of centriole formation and ciliogenesis in
mammalian lungs. J Cell Sci 1968, 3:207-230.
7. Bloodgood RA: Sensory reception is an attribute of both primary cilia
and motile cilia. J Cell Sci 2010, 123:505-509.
8. Nonaka S, Tanaka Y, Okada Y, Takeda S, Harada A, Kanai Y, Kido M,
Hirokawa N: Randomization of left-right asymmetry due to loss of nodal
cilia generating leftward flow of extraembryonic fluid in mice lacking
KIF3B motor protein. Cell 1998, 95:829-837.
9. Cole DG, Diener DR, Himelblau AL, Beech PL, Fuster JC, Rosenbaum J:
Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT
particles contain proteins required for ciliary assembly in Caenorhabditis
elegans sensory neurons. J Cell Biol 1998, 141:993-1008.
10. Kosminski KG, Johnson KA, Forscher P, Rosenbaum JL: A motility in the
eukaryotic flagellum unrelated to flagellar beating. Proc Natl Acad Sci USA
1993, 90:5519-5523.
11. Barr MM, Sternberg PW: A polycystic kidney-disease gene homologue
required for male mating behaviour in C. elegans. Nature 1999,
401:386-389.
12. Murcia NS, Richards WG, Yoder BK, Mucenski ML, Dunlap JR, Woychik RP:
The Oak Ridge Polycystic Kidney (orpk) disease gene is required for left-
right axis determination. Development 2000, 127:2347-2355.
13. Pazour GJ, Dickert BL, Vucica Y, Seely ES, Rosenbaum JL, Witman GB,
Cole DG: Chlamydomonas IFT88 and its mouse homologue, polycystic
Figure 1 Publications on primary cilia (Source: PubMed).
Beales and Jackson Cilia 2012, 1:1
http://www.ciliajournal.com/content/1/1/1
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kidney disease gene tg737, are required for assembly of cilia and
flagella. J Cell Biol 2000, 151:709-718.
14. Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV:
Hedgehog signalling in the mouse requires intraflagellar transport
proteins. Nature 2003, 426:83-87.
doi:10.1186/2046-2530-1-1
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    • "The last 10 years have witnessed increased interest in the primary cilia (Beales & Jackson, 2012). The major causes of this resurgence are twofold; cilia are omnipresent and highly dynamic. "
    [Show abstract] [Hide abstract] ABSTRACT: Primary cilia are cell surface, microtubule-based organelles that dynamically extend from cells to receive and process molecular and mechanical signaling cues. In the last decade, this organelle has gained increasing popularity due to its ability to act as a cellular antenna, receive molecular stimuli, and respond to the cell's environment. A growing field of data suggests that various tissues utilize and interpret the loss of cilia in different ways. Thus, careful examination of the role of cilia on individual cell types and tissues is necessary. Neural crest cells (NCCs) are an excellent example of cells that survey their environment for developmental cues. In this review, we discuss how NCCs utilize primary cilia during their ontogenic development, paying special attention to the role primary cilia play in processing developmental signals required for NCC specification, migration, proliferation, and differentiation. We also discuss how the loss of functional cilia on cranial and trunk NCCs affects the development of various organ systems to which they contribute. A deeper understanding of ciliary function could contribute greatly to understanding the molecular mechanisms guiding NCC development and differentiation. Furthermore, superimposing the ciliary contribution on our current understanding of NCC development identifies new avenues for therapeutic intervention in neurocristopathies. © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Feb 2015
    • "hen Antoni van Leeuwenhoek—who is often considered to be the 'Father of Microbiology'—looked down his microscope in 1675, he saw that some single-celled microbes had hair-like projections that moved with a sweeping motion. These organelles later came to be known as cilia, and they have been studied by countless biologists ever since (Beales and Jackson, 2012). These investigations have revealed that cilia can have a range of different structures and perform many different functions. "
    [Show abstract] [Hide abstract] ABSTRACT: Advances in sample preparation and electron microscopy have allowed the structure of cilia to be explored at an unprecedented level of detail.
    Full-text · Article · Mar 2014
    • "This is perhaps an appropriate denotation for a biological appendage found on the surface of a variety of eukaryotic cells, with a fascinating and still not fully understood relationship between internal structure and biological function [2]. Cilia not only have the capacity to transport surrounding fluids by means of periodic movements but they also play important sensory roles [1, 3]. Remarkably, their basic morphology and internal structure (the so-called axoneme), which is the same as in all eukaryotic flagella, has been conserved throughout evolution [4]. "
    [Show abstract] [Hide abstract] ABSTRACT: Cilia and flagella are hair-like appendages that protrude from the surface of a variety of eukaryotic cells and deform in a wavelike fashion to transport fluids and propel cells. Motivated by the ubiquity of non-Newtonian fluids in biology, we address mathematically the role of shear-dependent viscosities on both the waving flagellar locomotion and ciliary transport by metachronal waves. Using a two-dimensional waving sheet as model for the kinematics of a flagellum or an array of cilia, and allowing for both normal and tangential deformation of the sheet, we calculate the flow field induced by a small-amplitude deformation of the sheet in a generalized Newtonian Carreau fluid up to order four in the dimensionless waving amplitude. Shear-thinning and shear-thickening fluids are seen to always induce opposite effects. When the fluid is shear-thinning, the rate of working of the sheet against the fluid is always smaller than in the Newtonian fluid, and the largest gain is obtained for antiplectic metachronal waves. Considering a variety of deformation kinematics for the sheet, we further show that in all cases transport by the sheet is more efficiency in a shear-thinning fluid, and in most cases the transport speed in the fluid is also increased. Comparing the order of magnitude of the shear-thinning contributions with past work on elastic effects as well as the magnitude of the Newtonian contributions, our theoretical results suggest that the impact of shear-dependent viscosities on transport could play a major biological role.
    Full-text · Article · Mar 2014
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