Cilia orientation and the fluid mechanics of development

Marshall, Wallace F.; Kintner, Christopher R.

doi:10.1016/j.ceb.2007.11.009

Cited by 120 publications

(112 citation statements)

References 45 publications

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“…Using cell biological, genetic and modeling approaches, several studies in recent years have begun to provide us with mechanistic insights into how this is achieved. It appears that a combination of the planar cell polarity (PCP) pathway, long-range positional cues and the fluid flow itself that is generated by ciliary activity functions to position the cilia in the appropriate orientation relative to tissue axes, so that their synchronized beating can produce the effective stroke in the correct direction (Marshall and Kintner, 2008;Wallingford, 2010).…”

Section: Discussionmentioning

confidence: 99%

Cilia-driven fluid flow as an epigenetic cue for otolith biomineralization on sensory hair cells of the inner ear

Lau

et al. 2011

Development

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SUMMARYCiliary motility is necessary for many developmental and physiological processes in animals. In zebrafish, motile cilia are thought to be required for the deposition of otoliths, which comprise crystals of protein and calcium carbonate, on hair cells of the inner ear. The identity of the motile cilia and their role in otolith biogenesis, however, remain controversial. Here, we show that the ear vesicle differentiates numerous motile cilia, the spatial distribution of which changes as a function of the expression pattern of the ciliogenic gene foxj1b. By contrast, the hair cells develop immotile kinocilia that serve as static tethers for otolith crystallization. In ears devoid of all cilia, otoliths can form but they are of irregular shapes and sizes and appear to attach instead to the hair cell apical membranes. Moreover, overproduction of motile cilia also disrupts otolith deposition through sustained agitation of the precursor particles. Therefore, the correct spatial and temporal distribution of the motile cilia is crucial for proper otolith formation. Our findings support the view that the hair cells express a binding factor for the otolith precursors, while the motile cilia ensure that the precursors do not sediment prematurely and are efficiently directed towards the hair cells. We also provide evidence that the kinocilia are modified motile cilia that depend on Foxj1b for their differentiation. We propose that in hair cells, a Foxj1b-dependent motile ciliogenic program is altered by the proneural Atoh proteins to promote the differentiation of immotile kinocilia.

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Section: Discussionmentioning

confidence: 99%

Cilia-driven fluid flow as an epigenetic cue for otolith biomineralization on sensory hair cells of the inner ear

Lau

et al. 2011

Development

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“…Primary monocilia, present in most cells, lack a central pair of microtubules (9+0 structure), and play several roles in mechanosensation and cell signaling. Nodal cilia have a 9+0 structure but, unlike primary cilia, they move and generate an asymmetric distribution of morphogenetic cues in the node, thereby contributing to laterality 2 . The third group is composed of motile 9+2 cilia that cover epithelial cells lining airways, reproductive tracts, and cerebral ventricles.…”

mentioning

confidence: 99%

Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus

et al. 2010

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Cilia are organelles that protrude from the apical surface of most eukaryotic cells. According to their structure and motility, they are classified into three groups 1 . Primary monocilia, present in most cells, lack a central pair of microtubules (9+0 structure), and play several roles in mechanosensation and cell signaling. Nodal cilia have a 9+0 structure but, unlike primary cilia, they move and generate an asymmetric distribution of morphogenetic cues in the node, thereby contributing to laterality 2 . The third group is composed of motile 9+2 cilia that cover epithelial cells lining airways, reproductive tracts, and cerebral ventricles. Motile cilia play crucial functions in clearing mucus and debris in the airways and may assist the transit of sperm and eggs in genital tracts [3][4] . In the early postnatal mammalian brain, neuroepithelial cells that line the cerebral ventricles leave the cell cycle and differentiate into a monolayer of ependymal cells. At the end of maturation, the apical surface of ependymal cells bears dozens of cilia that beat in coordinate manner to facilitate the circulation of the cerebrospinal fluid (CSF), from sites of production in choroid plexuses to sites of absorption in subarachnoid spaces. In mice, mutations in genes involved in the assembly or structure of ependymal cilia, such as Mdnah5 5 , Ift88 (also known as Tg737 or Polaris) 6 , and Hy3 7-8 affect cilia genesis, CSF dynamics, and result in hydrocephalus. Thus far, however, little is known about the genetic factors that govern ependymal cilia polarization and the relationship between the polarity and the development and function of these organelles.Planar cell polarity (PCP), also known as tissue polarity, controls the polarization of epithelial cells in a plane perpendicular to their apicobasal axis. It was initially described in Drosophila, where it affects the stereotypic arrangement of cuticular hairs, sensory bristles, and Supplementary Fig. 1a, b). RT-PCR and (Supplementary Fig. 1c).Using the knocked-in beta-galactosidase reporter, we monitored the expression of Celsr2 in heterozygous mice. Consistent with published data [24][25][26] , Celsr2 expression was detected in all brain areas, from E11.5 to P5 (Fig. 1a-h). Celsr2 mutant mice develop progressive hydrocephalusCelsr2 mutant mice were viable and fertile, except for some females that had vaginal atresia. At birth, their brain did not display any flagrant morphological abnormality, suggesting that Celsr2 is not critical for cerebral embryonic development. However, a progressive ventricular dilation appeared between P5 and P10 with variable severity between animals, and became evident at P21 (Fig. 2a,b).The lateral ventricles were enlarged, and the septum had an abnormal triangular shape, due to 6 6 reduction of the dorsal part of the lateral septum. We did not observe any stenosis or constriction at the level of the foramen of Monro or of the aqueduct. The subcommissural organ (SCO), a structure thought to play a role in non-communicating hydrocephalus, was...

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“…Cilia in the airway, oviduct, embryonic node, and ependyma generate extracellular flows of mucus and other fluids. In adults, these flows are required for proper tissue function-for example, the clearing of mucus from the airway-whereas in developing organisms, these flows provide directional cues for left-right symmetry breaking and cell migration (Sawamoto et al 2006, Marshall and Kintner 2008, Schneider et al 2010, Yoshiba and Hamada 2014. Cilia do not just generate mechanical forces but also sense forces.…”

Section: Cilia As Generators and Sensors Of Mechanical Forcementioning

confidence: 99%

“…This feedback loop is thought to help coordinate ciliary orientation so that cilia beat in a consistent direction. However, the ultimate input to this feedback system would be long-range developmental cues, such as planar cell polarity (Marshall and Kintner 2008).…”

Section: Cilia As Generators and Sensors Of Mechanical Forcementioning

confidence: 99%

Mechanobiology of Ciliogenesis

Ishikawa¹,

Marshall²

2014

BioScience

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Cilia are force-generating and -sensing organelles that serve as mechanical interfaces between the cell and the extracellular environment. Cilia are present in tissues that adaptively respond to mechanical loading and fluid flow, and defects in ciliary function can lead to diseases affecting these tissues. As might be expected for a mechanical interface, the formation of cilia is, itself, regulated by mechanical forces, and these links between mechanics and ciliary formation are providing new entry points for dissecting the regulatory pathways of ciliogenesis.

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Cilia orientation and the fluid mechanics of development

Cited by 120 publications

References 45 publications

Cilia-driven fluid flow as an epigenetic cue for otolith biomineralization on sensory hair cells of the inner ear

Cilia-driven fluid flow as an epigenetic cue for otolith biomineralization on sensory hair cells of the inner ear

Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus

Mechanobiology of Ciliogenesis

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